Molecular and cellular mechanisms of spastin in neural development and disease (Review)

Liu,Qiuling; Zhang,Guowei; Ji,Zhisheng; Lin,Hongsheng

doi:10.3892/ijmm.2021.5051

Molecular and cellular mechanisms of spastin in neural development and disease (Review)

Authors:
- Qiuling Liu
- Guowei Zhang
- Zhisheng Ji
- Hongsheng Lin
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Affiliations: Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China, Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, P.R. China
Published online on: October 19, 2021 https://doi.org/10.3892/ijmm.2021.5051
Article Number: 218
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Spastin is a microtubule (MT)‑severing enzyme identified from mutations of hereditary spastic paraplegia in 1999 and extensive studies indicate its vital role in various cellular activities. In the past two decades, efforts have been made to understand the underlying molecular mechanisms of how spastin is linked to neural development and disease. Recent studies on spastin have unraveled the mechanistic processes of its MT‑severing activity and revealed that spastin acts as an MT amplifier to mediate its remodeling, thus providing valuable insight into the molecular roles of spastin under physiological conditions. In addition, recent research has revealed multiple novel molecular mechanisms of spastin in cellular biological pathways, including endoplasmic reticulum shaping, calcium trafficking, fatty acid trafficking, as well as endosomal fission and trafficking. These processes are closely involved in axonal and dendritic development and maintenance. The current review presents recent biological advances regarding the molecular mechanisms of spastin at the cellular level and provides insight into how it affects neural development and disease.

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1	Shribman S, Reid E, Crosby AH, Houlden H and Warner TT: Hereditary spastic paraplegia: From diagnosis to emerging therapeutic approaches. Lancet Neurol. 18:1136–1146. 2019. View Article : Google Scholar : PubMed/NCBI
2	Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmüller C, Kurzwelly D, Henkel D, et al: Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients. Ann Neurol. 79:646–658. 2016. View Article : Google Scholar
3	Solowska JM and Baas PW: Hereditary spastic paraplegia SPG4: What is known and not known about the disease. Brain. 138:2471–2484. 2015. View Article : Google Scholar : PubMed/NCBI
4	Fink JK: Hereditary spastic paraplegia: Clinico-pathologic features and emerging molecular mechanisms. Acta Neuropathol. 126:307–328. 2013. View Article : Google Scholar
5	Salinas S, Carazo-Salas RE, Proukakis C, Schiavo G and Warner TT: Spastin and microtubules: Functions in health and disease. J Neurosci Res. 85:2778–2782. 2007. View Article : Google Scholar : PubMed/NCBI
6	Solowska JM, Morfini G, Falnikar A, Himes BT, Brady ST, Huang D and Baas PW: Quantitative and functional analyses of spastin in the nervous system: Implications for hereditary spastic paraplegia. J Neurosci. 28:2147–2157. 2008. View Article : Google Scholar : PubMed/NCBI
7	Deluca GC, Ebers GC and Esiri MM: The extent of axonal loss in the long tracts in hereditary spastic paraplegia. Neuropathol Appl Neurobiol. 30:576–584. 2004. View Article : Google Scholar
8	Lumb JH, Connell JW, Allison R and Reid E: The AAA ATPase spastin links microtubule severing to membrane modelling. Biochim Biophys Acta. 1823:192–197. 2012. View Article : Google Scholar
9	Schickel J, Pamminger T, Ehrsam A, Münch S, Huang X, Klopstock T, Kurlemann G, Hemmerich P, Dubiel W, Deufel T and Beetz C: Isoform-specific increase of spastin stability by N-terminal missense variants including intragenic modifiers of SPG4 hereditary spastic paraplegia. Eur J Neurol. 14:1322–1328. 2007. View Article : Google Scholar
10	Havlicek S, Kohl Z, Mishra HK, Prots I, Eberhardt E, Denguir N, Wend H, Plötz S, Boyer L, Marchetto MC, et al: Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons. Hum Mol Genet. 23:2527–2541. 2014. View Article : Google Scholar : PubMed/NCBI
11	Arribat Y, Grepper D, Lagarrigue S, Qi T, Cohen S and Amati F: Spastin mutations impair coordination between lipid droplet dispersion and reticulum. PLoS Genet. 16:e10086652020. View Article : Google Scholar :
12	Park SH, Zhu PP, Parker RL and Blackstone C: Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network. J Clin Invest. 120:1097–1110. 2010. View Article : Google Scholar
13	Chang CL, Weigel AV, Ioannou MS, Pasolli HA, Xu CS, Peale DR, Shtengel G, Freeman M, Hess HF, Blackstone C, et al: Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III. J Cell Biol. 218:2583–2599. 2019. View Article : Google Scholar : PubMed/NCBI
14	Vietri M, Radulovic M and Stenmark H: The many functions of ESCRTs. Nat Rev Mol Cell Biol. 21:25–42. 2020. View Article : Google Scholar
15	Guo EZ and Xu Z: Distinct mechanisms of recognizing endosomal sorting complex required for transport III (ESCRT-III) protein IST1 by different microtubule interacting and trafficking (MIT) domains. J Biol Chem. 290:8396–8408. 2015. View Article : Google Scholar : PubMed/NCBI
16	Connell JW, Allison RJ, Rodger CE, Pearson G, Zlamalova E and Reid E: ESCRT-III-associated proteins and spastin inhibit protrudin-dependent polarised membrane traffic. Cell Mol Life Sci. 77:2641–2658. 2020. View Article : Google Scholar
17	Allison R, Lumb JH, Fassier C, Connell JW, Ten Martin D, Seaman MN, Hazan J and Reid E: An ESCRT-spastin interaction promotes fission of recycling tubules from the endosome. J Cell Biol. 202:527–543. 2013. View Article : Google Scholar : PubMed/NCBI
18	Allison R, Edgar JR, Pearson G, Rizo T, Newton T, Günther S, Berner F, Hague J, Connell JW, Winkler J, et al: Defects in ER-endosome contacts impact lysosome function in hereditary spastic paraplegia. J Cell Biol. 216:1337–1355. 2017. View Article : Google Scholar :
19	Leo L, Weissmann C, Burns M, Kang M, Song Y, Qiang L, Brady ST, Baas PW and Morfini G: Mutant spastin proteins promote deficits in axonal transport through an isoform-specific mechanism involving casein kinase 2 activation. Hum Mol Genet. 26:2321–2334. 2017. View Article : Google Scholar
20	Kasher PR, De Vos KJ, Wharton SB, Manser C, Bennett EJ, Bingley M, Wood JD, Milner R, McDermott CJ, Miller CC, et al: Direct evidence for axonal transport defects in a novel mouse model of mutant spastin-induced hereditary spastic paraplegia (HSP) and human HSP patients. J Neurochem. 110:34–44. 2009. View Article : Google Scholar : PubMed/NCBI
21	Jeong B, Kim TH, Kim DS, Shin WH, Lee JR, Kim NS and Lee DY: Spastin contributes to neural development through the regulation of microtubule dynamics in the primary cilia of neural stem cells. Neuroscience. 411:76–85. 2019. View Article : Google Scholar : PubMed/NCBI
22	Goyal U, Renvoisé B, Chang J and Blackstone C: Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon development. PLoS One. 9:e1124282014. View Article : Google Scholar : PubMed/NCBI
23	Ji Z, Zhang G, Chen L, Li J, Yang Y, Cha C, Zhang J, Lin H and Guo G: Spastin interacts with CRMP5 to promote neurite outgrowth by controlling the microtubule dynamics. Dev Neurobiol. 78:1191–1205. 2018. View Article : Google Scholar : PubMed/NCBI
24	Wood JD, Landers JA, Bingley M, McDermott CJ, Thomas-McArthur V, Gleadall LJ, Shaw PJ and Cunliffe VT: The microtubule-severing protein Spastin is essential for axon outgrowth in the zebrafish embryo. Hum Mol Genet. 15:2763–2771. 2006. View Article : Google Scholar : PubMed/NCBI
25	Lopes AT, Hausrat TJ, Heisler FF, Gromova KV, Lombino FL, Fischer T, Ruschkies L, Breiden P, Thies E, Hermans-Borgmeyer I, et al: Spastin depletion increases tubulin polyglutamylation and impairs kinesin-mediated neuronal transport, leading to working and associative memory deficits. PLoS Biol. 18:e30008202020. View Article : Google Scholar :
26	Ji ZS, Liu QL, Zhang JF, Yang YH, Li J, Zhang GW, Tan MH, Lin HS and Guo GQ: SUMOylation of spastin promotes the internalization of GluA1 and regulates dendritic spine morphology by targeting microtubule dynamics. Neurobiol Dis. 146:1051332020. View Article : Google Scholar : PubMed/NCBI
27	Sherwood NT, Sun Q, Xue M, Zhang B and Zinn K: Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function. PLoS Biol. 2:e4292004. View Article : Google Scholar : PubMed/NCBI
28	Roll-Mecak A and Vale RD: Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin. Nature. 451:363–367. 2008. View Article : Google Scholar
29	Kuo YW, Trottier O, Mahamdeh M and Howard J: Spastin is a dual-function enzyme that severs microtubules and promotes their regrowth to increase the number and mass of microtubules. Proc Natl Acad Sci USA. 116:5533–5541. 2019. View Article : Google Scholar : PubMed/NCBI
30	Connell JW, Lindon C, Luzio JP and Reid E: Spastin couples microtubule severing to membrane traffic in completion of cytokinesis and secretion. Traffic. 10:42–56. 2009. View Article : Google Scholar
31	Qiang L, Piermarini E and Baas PW: New hypothesis for the etiology of SPAST-based hereditary spastic paraplegia. Cytoskeleton (Hoboken). 76:289–297. 2019. View Article : Google Scholar
32	Sakoe K, Shioda N and Matsuura T: A newly identified NES sequence present in spastin regulates its subcellular localization and microtubule severing activity. Biochim Biophys Acta Mol Cell Res. 1868:1188622021. View Article : Google Scholar
33	Beetz C, Brodhun M, Moutzouris K, Kiehntopf M, Berndt A, Lehnert D, Deufel T, Bastmeyer M and Schickel J: Identification of nuclear localisation sequences in spastin (SPG4) using a novel Tetra-GFP reporter system. Biochem Biophys Res Commun. 318:1079–1084. 2004. View Article : Google Scholar
34	Monteonofrio L, Valente D, Rinaldo C and Soddu S: Extrachromosomal Histone H2B contributes to the formation of the abscission site for cell division. Cells. 8:13912019. View Article : Google Scholar
35	Sandate CR, Szyk A, Zehr EA, Lander GC and Roll-Mecak A: An allosteric network in spastin couples multiple activities required for microtubule severing. Nat Struct Mol Biol. 26:671–678. 2019. View Article : Google Scholar :
36	Han H, Schubert HL, McCullough J, Monroe N, Purdy MD, Yeager M, Sundquist WI and Hill CP: Structure of spastin bound to a glutamate-rich peptide implies a hand-over-hand mechanism of substrate translocation. J Biol Chem. 295:435–443. 2020. View Article : Google Scholar :
37	White SR, Evans KJ, Lary J, Cole JL and Lauring B: Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing. J Cell Biol. 176:995–1005. 2007. View Article : Google Scholar : PubMed/NCBI
38	Vemu A, Szczesna E, Zehr EA, Spector JO, Grigorieff N, Deaconescu AM and Roll-Mecak A: Severing enzymes amplify microtubule arrays through lattice GTP-tubulin incorporation. Science. 361:eaau15042018. View Article : Google Scholar
39	Kuo YW, Trottier O and Howard J: Predicted effects of severing enzymes on the length distribution and total mass of microtubules. Biophys J. 117:2066–2078. 2019. View Article : Google Scholar : PubMed/NCBI
40	Saltini M and Mulder BM: Critical threshold for microtubule amplification through templated severing. Phys Rev E. 101:0524052020. View Article : Google Scholar
41	Rao K, Stone MC, Weiner AT, Gheres KW, Zhou C, Deitcher DL, Levitan ES and Rolls MM: Spastin, atlastin, and ER relocalization are involved in axon but not dendrite regeneration. Mol Biol Cell. 27:3245–3256. 2016. View Article : Google Scholar : PubMed/NCBI
42	Vajente N, Norante R, Redolfi N, Daga A, Pizzo P and Pendin D: Microtubules stabilization by mutant spastin affects ER morphology and Ca²⁺ handling. Front Physiol. 10:15442019. View Article : Google Scholar
43	Pendin D, McNew JA and Daga A: Balancing ER dynamics: Shaping, bending, severing, and mending membranes. Curr Opin Cell Biol. 23:435–442. 2011. View Article : Google Scholar : PubMed/NCBI
44	Farías GG, Fréal A, Tortosa E, Stucchi R, Pan X, Portegies S, Will L, Altelaar M and Hoogenraad CC: Feedback-driven mechanisms between microtubules and the endoplasmic reticulum instruct neuronal polarity. Neuron. 102:184–201.e8. 2019. View Article : Google Scholar
45	Liu X, Guo X, Niu L, Li X, Sun F, Hu J, Wang X and Shen K: Atlastin-1 regulates morphology and function of endoplasmic reticulum in dendrites. Nat Commun. 10:5682019. View Article : Google Scholar : PubMed/NCBI
46	Hashimoto Y, Shirane M, Matsuzaki F, Saita S, Ohnishi T and Nakayama KI: Protrudin regulates endoplasmic reticulum morphology and function associated with the pathogenesis of hereditary spastic paraplegia. J Biol Chem. 289:12946–12961. 2014. View Article : Google Scholar :
47	Chang J, Lee S and Blackstone C: Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation. Proc Natl Acad Sci USA. 110:14954–14959. 2013. View Article : Google Scholar
48	Iworima DG, Pasqualotto BA and Rintoul GL: Kif5 regulates mitochondrial movement, morphology, function and neuronal survival. Mol Cell Neurosci. 72:22–33. 2016. View Article : Google Scholar : PubMed/NCBI
49	Matsuzaki F, Shirane M, Matsumoto M and Nakayama KI: Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation. Mol Biol Cell. 22:4602–4620. 2011. View Article : Google Scholar :
50	Shirane M, Wada M, Morita K, Hayashi N, Kunimatsu R, Matsumoto Y, Matsuzaki F, Nakatsumi H, Ohta K, Tamura Y and Nakayama KI: Protrudin and PDZD8 contribute to neuronal integrity by promoting lipid extraction required for endosome maturation. Nat Commun. 11:45762020. View Article : Google Scholar : PubMed/NCBI
51	Shirane M: Lipid transfer-dependent endosome maturation mediated by protrudin and PDZD8 in neurons. Front Cell Dev Biol. 8:6156002020. View Article : Google Scholar
52	Zhang C, Li D, Ma Y, Yan J, Yang B, Li P, Yu A, Lu C and Ma X: Role of spastin and protrudin in neurite outgrowth. J Cell Biochem. 113:2296–2307. 2012. View Article : Google Scholar
53	Olzmann JA and Carvalho P: Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 20:137–155. 2019. View Article : Google Scholar :
54	Walther TC, Chung J and Farese RV Jr: Lipid droplet biogenesis. Annu Rev Cell Dev Biol. 33:491–510. 2017. View Article : Google Scholar
55	Welte MA and Gould AP: Lipid droplet functions beyond energy storage. Biochim Biophys Acta Mol Cell Biol Lipids. 1862:1260–1272. 2017. View Article : Google Scholar : PubMed/NCBI
56	Velázquez AP, Tatsuta T, Ghillebert R, Drescher I and Graef M: Lipid droplet-mediated ER homeostasis regulates autophagy and cell survival during starvation. J Cell Biol. 212:621–631. 2016. View Article : Google Scholar
57	Papadopoulos C, Orso G, Mancuso G, Herholz M, Gumeni S, Tadepalle N, Jüngst C, Tzschichholz A, Schauss A, Höning S, et al: Spastin binds to lipid droplets and affects lipid metabolism. PLoS Genet. 11:e10051492015. View Article : Google Scholar :
58	Vietri M, Schink KO, Campsteijn C, Wegner CS, Schultz SW, Christ L, Thoresen SB, Brech A, Raiborg C and Stenmark H: Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. Nature. 522:231–235. 2015. View Article : Google Scholar
59	Reid E, Connell J, Edwards TL, Duley S, Brown SE and Sanderson CM: The hereditary spastic paraplegia protein spastin interacts with the ESCRT-III complex-associated endosomal protein CHMP1B. Hum Mol Genet. 14:19–38. 2005. View Article : Google Scholar
60	Christ L, Raiborg C, Wenzel EM, Campsteijn C and Stenmark H: Cellular functions and molecular mechanisms of the ESCRT membrane-scission machinery. Trends Biochem Sci. 42:42–56. 2017. View Article : Google Scholar
61	Henne WM, Buchkovich NJ and Emr SD: The ESCRT pathway. Dev Cell. 21:77–91. 2011. View Article : Google Scholar : PubMed/NCBI
62	Pisciottani A, Biancolillo L, Ferrara M, Valente D, Sardina F, Monteonofrio L, Camerini S, Crescenzi M, Soddu S and Rinaldo C: HIPK2 phosphorylates the microtubule-severing enzyme spastin at S268 for abscission. Cells. 8:6842019. View Article : Google Scholar :
63	Scott CC, Vacca F and Gruenberg J: Endosome maturation, transport and functions. Semin Cell Dev Biol. 31:2–10. 2014. View Article : Google Scholar
64	Tu Y, Zhao L, Billadeau DD and Jia D: Endosome-to-TGN trafficking: Organelle-vesicle and organelle-organelle interactions. Front Cell Dev Biol. 8:1632020. View Article : Google Scholar : PubMed/NCBI
65	Wang J, Fedoseienko A, Chen B, Burstein E, Jia D and Billadeau DD: Endosomal receptor trafficking: Retromer and beyond. Traffic. 19:578–590. 2018. View Article : Google Scholar :
66	Vagnozzi AN and Praticò D: Endosomal sorting and trafficking, the retromer complex and neurodegeneration. Mol Psychiatry. 24:857–868. 2019. View Article : Google Scholar :
67	Allison R, Edgar JR and Reid E: Spastin MIT Domain Disease-Associated mutations disrupt lysosomal function. Front Neurosci. 13:11792019. View Article : Google Scholar :
68	Skjeldal FM, Strunze S, Bergeland T, Walseng E, Gregers TF and Bakke O: The fusion of early endosomes induces molecular-motor-driven tubule formation and fission. J Cell Sci. 125:1910–1919. 2012.
69	Hoyer MJ, Chitwood PJ, Ebmeier CC, Striepen JF, Qi RZ, Old WM and Voeltz GK: A novel class of ER membrane proteins regulates ER-associated endosome fission. Cell. 175:254–265.e14. 2018. View Article : Google Scholar : PubMed/NCBI
70	Raiborg C, Wenzel EM, Pedersen NM, Olsvik H, Schink KO, Schultz SW, Vietri M, Nisi V, Bucci C, Brech A, et al: Repeated ER-endosome contacts promote endosome translocation and neurite outgrowth. Nature. 520:234–238. 2015. View Article : Google Scholar
71	Elbaz-Alon Y, Guo Y, Segev N, Harel M, Quinnell DE, Geiger T, Avinoam O, Li D and Nunnari J: PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria. Nat Commun. 11:36452020. View Article : Google Scholar : PubMed/NCBI
72	Joshi AS, Nebenfuehr B, Choudhary V, Satpute-Krishnan P, Levine TP, Golden A and Prinz WA: Lipid droplet and peroxisome biogenesis occur at the same ER subdomains. Nat Commun. 9:29402018. View Article : Google Scholar :
73	Joshi AS and Cohen S: Lipid droplet and peroxisome biogenesis: Do they go hand-in-hand? Front Cell Dev Biol. 7:922019. View Article : Google Scholar
74	Walker CL, Pomatto LCD, Tripathi DN and Davies KJA: Redox regulation of homeostasis and proteostasis in peroxisomes. Physiol Rev. 98:89–115. 2018. View Article : Google Scholar
75	Islinger M, Voelkl A, Fahimi HD and Schrader M: The peroxisome: An update on mysteries 2.0. Histochem Cell Biol. 150:443–471. 2018. View Article : Google Scholar :
76	Henne WM: Spastin joins LDs and peroxisomes in the interorganelle contact ballet. J Cell Biol. 218:2439–2441. 2019. View Article : Google Scholar :
77	Riano E, Martignoni M, Mancuso G, Cartelli D, Crippa F, Toldo I, Siciliano G, Di Bella D, Taroni F, Bassi MT, et al: Pleiotropic effects of spastin on neurite growth depending on expression levels. J Neurochem. 108:1277–1288. 2009. View Article : Google Scholar
78	Denton KR, Lei L, Grenier J, Rodionov V, Blackstone C and Li XJ: Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia. Stem Cells. 32:414–423. 2014. View Article : Google Scholar
79	Henson BJ, Zhu W, Hardaway K, Wetzel JL, Stefan M, Albers KM and Nicholls RD: Transcriptional and post-transcriptional regulation of SPAST, the gene most frequently mutated in hereditary spastic paraplegia. PLoS One. 7:e365052012. View Article : Google Scholar : PubMed/NCBI
80	Jiang T, Cai Z, Ji Z, Zou J, Liang Z, Zhang G, Liang Y, Lin H and Tan M: The lncRNA MALAT1/miR-30/Spastin axis regulates hippocampal neurite outgrowth. Front Cell Neurosci. 14:5557472020. View Article : Google Scholar
81	Nakazeki F, Tsuge I, Horie T, Imamura K, Tsukita K, Hotta A, Baba O, Kuwabara Y, Nishino T, Nakao T, et al: MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons. Clin Sci (Lond). 133:583–595. 2019. View Article : Google Scholar
82	Sardina F, Pisciottani A, Ferrara M, Valente D, Casella M, Crescenzi M, Peschiaroli A, Casali C, Soddu S, Grierson AJ and Rinaldo C: Spastin recovery in hereditary spastic paraplegia by preventing neddylation-dependent degradation. Life Sci Alliance. 3:e2020007992020. View Article : Google Scholar :
83	Tan R, Lam AJ, Tan T, Han J, Nowakowski DW, Vershinin M, Simó S, Ori-McKenney KM and McKenney RJ: Microtubules gate tau condensation to spatially regulate microtubule functions. Nat Cell Biol. 21:1078–1085. 2019. View Article : Google Scholar :
84	Jin Z, Shou HF, Liu JW, Jiang SS, Shen Y, Cheng WY and Gao LL: Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules. Zygote. 1–12. 2021. View Article : Google Scholar
85	Newton T, Allison R, Edgar JR, Lumb JH, Rodger CE, Manna PT, Rizo T, Kohl Z, Nygren AOH, Arning L, et al: Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia. Brain. 141:1286–1299. 2018. View Article : Google Scholar : PubMed/NCBI
86	Kapitein LC and Hoogenraad CC: Building the neuronal microtubule cytoskeleton. Neuron. 87:492–506. 2015. View Article : Google Scholar
87	Kelliher MT, Saunders HA and Wildonger J: Microtubule control of functional architecture in neurons. Curr Opin Neurobiol. 57:39–45. 2019. View Article : Google Scholar : PubMed/NCBI
88	Bond AM, Ming GL and Song H: Adult mammalian neural stem cells and neurogenesis: Five decades later. Cell Stem Cell. 17:385–395. 2015. View Article : Google Scholar :
89	Katsimpardi L and Lledo PM: Regulation of neurogenesis in the adult and aging brain. Curr Opin Neurobiol. 53:131–138. 2018. View Article : Google Scholar
90	McNally FJ and Roll-Mecak A: Microtubule-severing enzymes: From cellular functions to molecular mechanism. J Cell Biol. 217:4057–4069. 2018. View Article : Google Scholar : PubMed/NCBI
91	Kahn OI and Baas PW: Microtubules and growth cones: Motors drive the turn. Trends Neurosci. 39:433–440. 2016. View Article : Google Scholar :
92	Dent EW and Gertler FB: Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron. 40:209–227. 2003. View Article : Google Scholar
93	Lowery LA and Van Vactor D: The trip of the tip: Understanding the growth cone machinery. Nat Rev Mol Cell Biol. 10:332–343. 2009. View Article : Google Scholar : PubMed/NCBI
94	Dent EW, Gupton SL and Gertler FB: The growth cone cytoskeleton in axon outgrowth and guidance. Cold Spring Harb Perspect Biol. 3:a0018002011. View Article : Google Scholar
95	Rao AN and Baas PW: Polarity sorting of microtubules in the axon. Trends Neurosci. 41:77–88. 2018. View Article : Google Scholar
96	Tas RP, Chazeau A, Cloin BMC, Lambers MLA, Hoogenraad CC and Kapitein LC: Differentiation between oppositely oriented microtubules controls polarized neuronal transport. Neuron. 96:1264–1271.e5. 2017. View Article : Google Scholar : PubMed/NCBI
97	Claudiani P, Riano E, Errico A, Andolfi G and Rugarli EI: Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus. Exp Cell Res. 309:358–369. 2005. View Article : Google Scholar
98	Butler R, Wood JD, Landers JA and Cunliffe VT: Genetic and chemical modulation of spastin-dependent axon outgrowth in zebrafish embryos indicates a role for impaired microtubule dynamics in hereditary spastic paraplegia. Dis Model Mech. 3:743–751. 2010. View Article : Google Scholar : PubMed/NCBI
99	Karabay A, Yu W, Solowska JM, Baird DH and Baas PW: Axonal growth is sensitive to the levels of katanin, a protein that severs microtubules. J Neurosci. 24:5778–5788. 2004. View Article : Google Scholar
100	Yu W, Qiang L, Solowska JM, Karabay A, Korulu S and Baas PW: The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches. Mol Biol Cell. 19:1485–1498. 2008. View Article : Google Scholar : PubMed/NCBI
101	Conde C and Cáceres A: Microtubule assembly, organization and dynamics in axons and dendrites. Nat Rev Neurosci. 10:319–332. 2009. View Article : Google Scholar
102	Herms J and Dorostkar MM: Dendritic spine pathology in neurodegenerative diseases. Annu Rev Pathol. 11:221–250. 2016. View Article : Google Scholar : PubMed/NCBI
103	Stein IS and Zito K: Dendritic spine elimination: Molecular mechanisms and implications. Neuroscientist. 25:27–47. 2019. View Article : Google Scholar
104	Park M: AMPA receptor trafficking for postsynaptic potentiation. Front Cell Neurosci. 12:3612018.
105	Chater TE and Goda Y: The role of AMPA receptors in postsynaptic mechanisms of synaptic plasticity. Front Cell Neurosci. 8:4012014. View Article : Google Scholar
106	Hanley JG: AMPA receptor trafficking pathways and links to dendritic spine morphogenesis. Cell Adh Migr. 2:276–282. 2008. View Article : Google Scholar
107	Dong H, O'Brien RJ, Fung ET, Lanahan AA, Worley PF and Huganir RL: GRIP: A synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature. 386:279–284. 1997. View Article : Google Scholar
108	Nakajima K, Yin X, Takei Y, Seog DH, Homma N and Hirokawa N: Molecular motor KIF5A is essential for GABA(A) receptor transport, and KIF5A deletion causes epilepsy. Neuron. 76:945–961. 2012. View Article : Google Scholar : PubMed/NCBI
109	Jaworski J, Kapitein LC, Gouveia SM, Dortland BR, Wulf PS, Grigoriev I, Camera P, Spangler SA, Di Stefano P, Demmers J, et al: Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity. Neuron. 61:85–100. 2009. View Article : Google Scholar : PubMed/NCBI
110	Okabe S and Hirokawa N: Axonal transport. Curr Opin Cell Biol. 1:91–97. 1989. View Article : Google Scholar : PubMed/NCBI
111	Millecamps S and Julien JP: Axonal transport deficits and neurodegenerative diseases. Nat Rev Neurosci. 14:161–176. 2013. View Article : Google Scholar : PubMed/NCBI
112	Gibbs KL, Greensmith L and Schiavo G: Regulation of axonal transport by protein kinases. Trends Biochem Sci. 40:597–610. 2015. View Article : Google Scholar : PubMed/NCBI
113	Guedes-Dias P and Holzbaur ELF: Axonal transport: Driving synaptic function. Science. 366:eaaw99972019. View Article : Google Scholar : PubMed/NCBI
114	Cyr JL and Brady ST: Molecular motors in axonal transport. Cellular and molecular biology of kinesin Mol Neurobiol. 6:137–155. 1992.
115	Fuerst JC, Henkel AW, Stroebel A, Welzel O, Groemer TW, Kornhuber J and Bönsch D: Distinct intracellular vesicle transport mechanisms are selectively modified by spastin and spastin mutations. J Cell Physiol. 226:362–368. 2011. View Article : Google Scholar
116	McDermott CJ, Grierson AJ, Wood JD, Bingley M, Wharton SB, Bushby KM and Shaw PJ: Hereditary spastic paraparesis: Disrupted intracellular transport associated with spastin mutation. Ann Neurol. 54:748–759. 2003. View Article : Google Scholar : PubMed/NCBI
117	Wali G, Sutharsan R, Fan Y, Stewart R, Tello Velasquez J, Sue CM, Crane DI and Mackay-Sim A: Mechanism of impaired microtubule-dependent peroxisome trafficking and oxidative stress in SPAST-mutated cells from patients with Hereditary Spastic Paraplegia. Sci Rep. 6:270042016. View Article : Google Scholar : PubMed/NCBI
118	Wali G, Liyanage E, Blair NF, Sutharsan R, Park JS, Mackay-Sim A and Sue CM: Oxidative stress-induced axon fragmentation is a consequence of reduced axonal transport in hereditary spastic paraplegia SPAST patient neurons. Front Neurosci. 14:4012020. View Article : Google Scholar :
119	Plaud C, Joshi V, Marinello M, Pastré D, Galli T, Curmi PA and Burgo A: Spastin regulates VAMP7-containing vesicles trafficking in cortical neurons. Biochim Biophys Acta Mol Basis Dis. 1863:1666–1677. 2017. View Article : Google Scholar
120	Jardin N, Giudicelli F, Ten Martín D, Vitrac A, De Gois S, Allison R, Houart C, Reid E, Hazan J and Fassier C: BMP- and neuropilin 1-mediated motor axon navigation relies on spastin alternative translation. Development. 145:dev1627012018. View Article : Google Scholar : PubMed/NCBI
121	Plaud C, Joshi V, Kajevu N, Poüs C, Curmi PA and Burgo A: Functional differences of short and long isoforms of spastin harboring missense mutation. Dis Model Mech. 11:dmm0337042018. View Article : Google Scholar
122	Öztürk Z, O'Kane CJ and Pérez-Moreno JJ: Axonal endoplasmic reticulum dynamics and its roles in neurodegeneration. Front Neurosci. 14:482020. View Article : Google Scholar : PubMed/NCBI
123	Henne WM, Liou J and Emr SD: Molecular mechanisms of inter-organelle ER-PM contact sites. Curr Opin Cell Biol. 35:123–130. 2015. View Article : Google Scholar
124	Phillips MJ and Voeltz GK: Structure and function of ER membrane contact sites with other organelles. Nat Rev Mol Cell Biol. 17:69–82. 2016. View Article : Google Scholar
125	Chung WY, Jha A, Ahuja M and Muallem S: Ca²⁺ influx at the ER/PM junctions. Cell Calcium. 63:29–32. 2017. View Article : Google Scholar : PubMed/NCBI
126	Friel D: Interplay between ER Ca²⁺ uptake and release fluxes in neurons and its impact on [Ca²⁺] dynamics. Biol Res. 37:665–674. 2004. View Article : Google Scholar
127	Rehbach K, Kesavan J, Hauser S, Ritzenhofen S, Jungverdorben J, Schüle R, Schöls L, Peitz M and Brüstle O: Multiparametric rapid screening of neuronal process pathology for drug target identification in HSP patient-specific neurons. Sci Rep. 9:96152019. View Article : Google Scholar : PubMed/NCBI
128	Julien C, Lissouba A, Madabattula S, Fardghassemi Y, Rosenfelt C, Androschuk A, Strautman J, Wong C, Bysice A, O'sullivan J, et al: Conserved pharmacological rescue of hereditary spastic paraplegia-related phenotypes across model organisms. Hum Mol Genet. 25:1088–1099. 2016. View Article : Google Scholar :
129	Connell JW, Allison R and Reid E: Quantitative gait analysis using a motorized treadmill system sensitively detects motor abnormalities in mice expressing ATPase defective spastin. PLoS One. 11:e01524132016. View Article : Google Scholar :
130	Qiang L, Piermarini E, Muralidharan H, Yu W, Leo L, Hennessy LE, Fernandes S, Connors T, Yates PL, Swift M, et al: Hereditary spastic paraplegia: Gain-of-function mechanisms revealed by new transgenic mouse. Hum Mol Genet. 28:1136–1152. 2019. View Article : Google Scholar
131	Solowska JM, D'Rozario M, Jean DC, Davidson MW, Marenda DR and Baas PW: Pathogenic mutation of spastin has gain-of-function effects on microtubule dynamics. J Neurosci. 34:1856–1867. 2014. View Article : Google Scholar : PubMed/NCBI
132	Yip AG, Dürr A, Marchuk DA, Ashley-Koch A, Hentati A, Rubinsztein DC and Reid E: Meta-analysis of age at onset in spastin-associated hereditary spastic paraplegia provides no evidence for a correlation with mutational class. J Med Genet. 40:e1062003. View Article : Google Scholar
133	Wu F, Qiu J, Fan Y, Zhang Q, Cheng B, Wu Y and Bai B: Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating Gα_i/Gα_q-CK2 signaling in ischemic stroke. Exp Neurol. 302:136–144. 2018. View Article : Google Scholar : PubMed/NCBI
134	Manni S, Brancalion A, Tubi LQ, Colpo A, Pavan L, Cabrelle A, Ave E, Zaffino F, Di Maira G, Ruzzene M, et al: Protein kinase CK2 protects multiple myeloma cells from ER stress-induced apoptosis and from the cytotoxic effect of HSP90 inhibition through regulation of the unfolded protein response. Clin Cancer Res. 18:1888–1900. 2012. View Article : Google Scholar
135	Hessenauer A, Schneider CC, Götz C and Montenarh M: CK2 inhibition induces apoptosis via the ER stress response. Cell Signal. 23:145–151. 2011. View Article : Google Scholar
136	Fassier C, Tarrade A, Peris L, Courageot S, Mailly P, Dalard C, Delga S, Roblot N, Lefèvre J, Job D, et al: Microtubule-targeting drugs rescue axonal swellings in cortical neurons from spastin knockout mice. Dis Model Mech. 6:72–83. 2013.