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Targeted disruption of Rab1a causes early embryonic lethality

  • Authors:
    • Yin Wu
    • Darong Yang
    • Guo-Yun Chen
  • View Affiliations / Copyright

    Affiliations: Children's Foundation Research Institute at Le Bonheur Children's Hospital, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 46
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    Published online on: February 7, 2022
       https://doi.org/10.3892/ijmm.2022.5101
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Abstract

Guanosine nucleotide diphosphate (GDP) dissociation inhibitor 2 (GDI2) regulates the GDP/guanosine triphosphate (GTP) exchange reaction of Rab proteins by inhibiting the dissociation of GDP and the subsequent binding of GTP. The present study aimed to determine the function of Rab1a in vivo, and thus generated mice with a trapped Rab1a gene. It was demonstrated that Rab1a is essential for embryonic development. It was also found that one functional Rab1a allele was sufficient for development in a heterozygous murine embryo, whereas a double mutant led to embryonic lethality. The dissection of uteri on embryonic day (E)10.5‑14.5 yielded no homozygous embryos, indicating that homozygotes die between E10.5 to E11.5. The gene trap construct contains a β‑galactosidase/neomycin reporter gene, allowing for heterozygotes to be stained for β‑galactosidase to determine the tissue‑specific expression of Rab1a. Rab1a was found to be highly expressed in the small intestine of both adult mice and embryos, although its expression levels were low in the brains of embryos. Moreover, there was no significant change in cytokine production and survival in wild‑type and heterozygous Rab1a+/‑ mice following a challenge with lipopolysaccharide. On the whole, the present study demonstrates that the disruption of the Rab1a gene causes embryonic lethality and homozygotes die between E10.5 and E11.5, suggesting that Rab1a is essential for the early development of mouse embryos.
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View References

1 

Pfeffer SR: Rab GTPases: Specifying and deciphering organelle identity and function. Trends Cell Biol. 11:487–491. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Zerial M and McBride H: Rab proteins as membrane organizers. Nat Rev Mol Cell Biol. 2:107–117. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Tisdale EJ, Bourne JR, Khosravi-Far R, Der CJ and Balch WE: GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex. J Cell Biol. 119:749–761. 1992. View Article : Google Scholar : PubMed/NCBI

4 

Nuoffer C, Davidson HW, Matteson J, Meinkoth J and Balch WE: A GDP-bound of rab1 inhibits protein export from the endoplasmic reticulum and transport between Golgi compartments. J Cell Biol. 125:225–237. 1994. View Article : Google Scholar

5 

Zhuang X, Adipietro KA, Datta S, Northup JK and Ray K: Rab1 small GTP-binding protein regulates cell surface trafficking of the human calcium-sensing receptor. Endocrinology. 151:5114–5123. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Marie M, Dale HA, Sannerud R and Saraste J: The function of the intermediate compartment in pre-Golgi trafficking involves its stable connection with the centrosome. Mol Biol Cell. 20:4458–4470. 2009. View Article : Google Scholar :

7 

Wu G, Yussman MG, Barrett TJ, Hahn HS, Osinska H, Hilliard GM, Wang X, Toyokawa T, Yatani A, Lynch RA, et al: Increased myocardial Rab GTPase expression: A consequence and cause of cardiomyopathy. Circ Res. 89:1130–1137. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Machner MP and Isberg RR: A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science. 318:974–977. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Neunuebel MR, Chen Y, Gaspar AH, Backlund PS Jr, Yergey A and Machner MP: De-AMPylation of the small GTPase Rab1 by the pathogen Legionella pneumophila. Science. 333:453–456. 2011. View Article : Google Scholar :

10 

Tan Y and Luo ZQ: Legionella pneumophila SidD is a deAM-Pylase that modifies Rab1. Nature. 475:506–509. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Sklan EH, Serrano RL, Einav S, Pfeffer SR, Lambright DG and Glenn JS: TBC1D20 is a Rab1 GTPase-activating protein that mediates hepatitis C virus replication. J Biol Chem. 282:36354–36361. 2007. View Article : Google Scholar

12 

Zhang X, Wang X, Yuan Z, Radford SJ, Liu C, Libutti SK and Zheng XF: Amino acids-Rab1A-mTORC1 signaling controls whole-body glucose homeostasis. Cell Rep. 34:1088302021. View Article : Google Scholar : PubMed/NCBI

13 

Thomas JD, Zhang YJ, Wei YH, Cho JH, Morris LE, Wang HY and Zheng XF: Rab1A is an mTORC1 activator and a colorectal oncogene. Cancer Cell. 26:754–769. 2014. View Article : Google Scholar

14 

Xu BH, Li XX, Yang Y, Zhang MY, Rao HL, Wang HY and Zheng XF: Aberrant amino acid signaling promotes growth and metastasis of hepatocellular carcinomas through Rab1A-dependent activation of mTORC1 by Rab1A. Oncotarget. 6:20813–20828. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Xu H, Qian M, Zhao B, Wu C, Maskey N, Song H, Li D, Song J, Hua K and Fang L: Inhibition of RAB1A suppresses epithelial-mesenchymal transition and proliferation of triple-negative breast cancer cells. Oncol Rep. 37:1619–1626. 2017. View Article : Google Scholar

16 

Takai Y, Sasaki T and Matozaki T: Small GTP-binding proteins. Physiol Rev. 81:153–208. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, Habuka M, Tahmasebpoor S, Danielsson A, Edlund K, et al: Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 13:397–406. 2014. View Article : Google Scholar :

18 

Wu Y, Yang D and Chen GY: The role of the Siglec-G ITIM domain during bacterial infection. Cell Mol Biol. 67:163–169. 2021. View Article : Google Scholar

19 

Chen GY, Muramatsu H, Kondo M, Kurosawa N, Miyake Y, Takeda N and Muramatsu T: Abnormalities caused by carbohydrate alterations in Ibeta6-N-acetylglucosaminyltransferase-deficient mice. Mol Cell Biol. 25:7828–7838. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Bundschu K, Knobeloch KP, Ullrich M, Schinke T, Amling M, Engelhardt CM, Renné T, Walter U and Schuh K: Gene disruption of Spred-2 causes dwarfism. J Biol Chem. 280:28572–28580. 2005. View Article : Google Scholar

21 

Chen GY, Brown NK, Wu W, Khedri Z, Yu H, Chen X, van de Vlekkert D, D'Azzo A, Zheng P and Liu Y: Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1. Elife. 3:e040662014. View Article : Google Scholar : PubMed/NCBI

22 

Wu Y, Yang D, Liu R, Wang L and Chen GY: Selective response to bacterial infection by regulating Siglec-E expression. iScience. 23:1014732020. View Article : Google Scholar :

23 

Chen GY, Chen X, King S, Cavassani KA, Cheng J, Zheng X, Cao H, Yu H, Qu J, Fang D, et al: Amelioration of sepsis by inhibiting sialidase-mediated disruption of the CD24-SiglecG interaction. Nat Biotechnol. 29:428–435. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Chen GY, Tang J, Zheng P and Liu Y: CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science. 323:1722–1725. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Chen WV and Soriano P: Gene trap mutagenesis in embryonic stem cells. Methods Enzymol. 365:367–386. 2003.PubMed/NCBI

26 

Friedrich G and Soriano P: Insertional mutagenesis by retro-viruses and promoter traps in embryonic stem cells. Methods Enzymol. 225:681–701. 1993. View Article : Google Scholar

27 

Stryke D, Kawamoto M, Huang CC, Johns SJ, King LA, Harper CA, Meng EC, Lee RE, Yee A, L'Italien L, et al: BayGenomics: A resource of insertional mutations in mouse embryonic stem cells. Nucleic Acids Res. 31:278–281. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Ayala J, Olofsson B, Touchot N, Zahraoui A, Tavitian A and Prochiantz A: Developmental and regional expression of three new members of the ras-gene family in the mouse brain. J Neurosci Res. 22:384–389. 1989. View Article : Google Scholar : PubMed/NCBI

29 

Olofsson B, Chardin P, Touchot N, Zahraoui A and Tavitian A: Expression of the ras-related ralA, rho12 and rab genes in adult mouse tissues. Oncogene. 3:231–234. 1988.PubMed/NCBI

30 

Said N, Sanchez-Carbayo M, Smith SC and Theodorescu D: RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration. J Clin Invest. 122:1503–1518. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Zhang Y, Wang L, Lv Y, Jiang C, Wu G, Dull RO, Minshall RD, Malik AB and Hu G: The GTPase Rab1 is required for NLRP3 inflammasome activation and inflammatory lung injury. J Immunol. 202:194–206. 2019. View Article : Google Scholar

32 

Maitre B, Magnenat S, Heim V, Ravanat C, Evans RJ, de la Salle H, Gachet C and Hechler B: The P2X1 receptor is required for neutrophil extravasation during lipopolysaccharide-induced lethal endotoxemia in mice. J Immunol. 194:739–749. 2015. View Article : Google Scholar

33 

Seabra MC and Wasmeier C: Controlling the location and activation of Rab GTPases. Curr Opin Cell Biol. 16:451–457. 2004. View Article : Google Scholar : PubMed/NCBI

34 

Le Y and Sauer B: Conditional gene knockout using cre recombinase. Methods Mol Biol. 136:477–485. 2000.PubMed/NCBI

35 

Sato T, Mushiake S, Kato Y, Sato K, Sato M, Takeda N, Ozono K, Miki K, Kubo Y, Tsuji A, et al: The Rab8 GTPase regulates apical protein localization in intestinal cells. Nature. 448:366–369. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Sobajima T, Yoshimura S, Iwano T, Kunii M, Watanabe M, Atik N, Mushiake S, Morii E, Koyama Y, Miyoshi E and Harada A: Rab11a is required for apical protein localisation in the intestine. Biol Open. 4:86–94. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Nam KT, Lee HJ, Smith JJ, Lapierre LA, Kamath VP, Chen X, Aronow BJ, Yeatman TJ, Bhartur SG, Calhoun BC, et al: Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas. J Clin Invest. 120:840–849. 2010. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wu Y, Yang D and Chen G: Targeted disruption of Rab1a causes early embryonic lethality. Int J Mol Med 49: 46, 2022.
APA
Wu, Y., Yang, D., & Chen, G. (2022). Targeted disruption of Rab1a causes early embryonic lethality. International Journal of Molecular Medicine, 49, 46. https://doi.org/10.3892/ijmm.2022.5101
MLA
Wu, Y., Yang, D., Chen, G."Targeted disruption of Rab1a causes early embryonic lethality". International Journal of Molecular Medicine 49.4 (2022): 46.
Chicago
Wu, Y., Yang, D., Chen, G."Targeted disruption of Rab1a causes early embryonic lethality". International Journal of Molecular Medicine 49, no. 4 (2022): 46. https://doi.org/10.3892/ijmm.2022.5101
Copy and paste a formatted citation
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Spandidos Publications style
Wu Y, Yang D and Chen G: Targeted disruption of Rab1a causes early embryonic lethality. Int J Mol Med 49: 46, 2022.
APA
Wu, Y., Yang, D., & Chen, G. (2022). Targeted disruption of Rab1a causes early embryonic lethality. International Journal of Molecular Medicine, 49, 46. https://doi.org/10.3892/ijmm.2022.5101
MLA
Wu, Y., Yang, D., Chen, G."Targeted disruption of Rab1a causes early embryonic lethality". International Journal of Molecular Medicine 49.4 (2022): 46.
Chicago
Wu, Y., Yang, D., Chen, G."Targeted disruption of Rab1a causes early embryonic lethality". International Journal of Molecular Medicine 49, no. 4 (2022): 46. https://doi.org/10.3892/ijmm.2022.5101
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