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

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

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

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

Fink JK: Hereditary spastic paraplegia: Clinico-pathologic features and emerging molecular mechanisms. Acta Neuropathol. 126:307–328. 2013. View Article : Google Scholar

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

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

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

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

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

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

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 :

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

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

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

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

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

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

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 :

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

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

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

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

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

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

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 :

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

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

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

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

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

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

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

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

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

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 :

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 :

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

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

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

Saltini M and Mulder BM: Critical threshold for microtubule amplification through templated severing. Phys Rev E. 101:0524052020. View Article : Google Scholar

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

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

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

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

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

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 :

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

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

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 :

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

Shirane M: Lipid transfer-dependent endosome maturation mediated by protrudin and PDZD8 in neurons. Front Cell Dev Biol. 8:6156002020. View Article : Google Scholar

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

Olzmann JA and Carvalho P: Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 20:137–155. 2019. View Article : Google Scholar :

Walther TC, Chung J and Farese RV Jr: Lipid droplet biogenesis. Annu Rev Cell Dev Biol. 33:491–510. 2017. View Article : Google Scholar

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

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

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 :

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

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

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

Henne WM, Buchkovich NJ and Emr SD: The ESCRT pathway. Dev Cell. 21:77–91. 2011. View Article : Google Scholar : PubMed/NCBI

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 :

Scott CC, Vacca F and Gruenberg J: Endosome maturation, transport and functions. Semin Cell Dev Biol. 31:2–10. 2014. View Article : Google Scholar

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

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 :

Vagnozzi AN and Praticò D: Endosomal sorting and trafficking, the retromer complex and neurodegeneration. Mol Psychiatry. 24:857–868. 2019. View Article : Google Scholar :

Allison R, Edgar JR and Reid E: Spastin MIT Domain Disease-Associated mutations disrupt lysosomal function. Front Neurosci. 13:11792019. View Article : Google Scholar :

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.

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

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

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

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 :

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

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

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 :

Henne WM: Spastin joins LDs and peroxisomes in the interorganelle contact ballet. J Cell Biol. 218:2439–2441. 2019. View Article : Google Scholar :

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

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

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

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

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

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 :

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 :

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

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

Kapitein LC and Hoogenraad CC: Building the neuronal microtubule cytoskeleton. Neuron. 87:492–506. 2015. View Article : Google Scholar

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

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 :

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

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

Kahn OI and Baas PW: Microtubules and growth cones: Motors drive the turn. Trends Neurosci. 39:433–440. 2016. View Article : Google Scholar :

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

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

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

Rao AN and Baas PW: Polarity sorting of microtubules in the axon. Trends Neurosci. 41:77–88. 2018. View Article : Google Scholar

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

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

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

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

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

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

Herms J and Dorostkar MM: Dendritic spine pathology in neurodegenerative diseases. Annu Rev Pathol. 11:221–250. 2016. View Article : Google Scholar : PubMed/NCBI

Stein IS and Zito K: Dendritic spine elimination: Molecular mechanisms and implications. Neuroscientist. 25:27–47. 2019. View Article : Google Scholar

Park M: AMPA receptor trafficking for postsynaptic potentiation. Front Cell Neurosci. 12:3612018.

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

Hanley JG: AMPA receptor trafficking pathways and links to dendritic spine morphogenesis. Cell Adh Migr. 2:276–282. 2008. View Article : Google Scholar

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

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

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

Okabe S and Hirokawa N: Axonal transport. Curr Opin Cell Biol. 1:91–97. 1989. View Article : Google Scholar : PubMed/NCBI

Millecamps S and Julien JP: Axonal transport deficits and neurodegenerative diseases. Nat Rev Neurosci. 14:161–176. 2013. View Article : Google Scholar : PubMed/NCBI

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

Guedes-Dias P and Holzbaur ELF: Axonal transport: Driving synaptic function. Science. 366:eaaw99972019. View Article : Google Scholar : PubMed/NCBI

Cyr JL and Brady ST: Molecular motors in axonal transport. Cellular and molecular biology of kinesin Mol Neurobiol. 6:137–155. 1992.

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

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

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

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 :

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

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

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

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

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

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

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

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

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

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 :

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 :

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

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

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

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

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

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

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.