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http://dx.doi.org/10.5352/JLS.2020.30.8.708

Deletion of the VPS26b-VPS29-VPS35 Retromer Complex Results in Learning Disabilities and Neurodegeneration  

Kim, Ekyune (College of Pharmacy, Daegu Catholic University)
Publication Information
Journal of Life Science / v.30, no.8, 2020 , pp. 708-712 More about this Journal
Abstract
Vacuolar protein sorting (VPS) 26b is a newly discovered member of the retromer complex; it is encoded by a single-copy gene located on mouse chromosome 9, and the complex has been reported as being composed of proteins VPS26, VPS29, and VPS35. We have previously shown that mice lacking VPS26b exhibited no significant body size or health issues. Although retromer components are widely expressed in mouse tissue, their roles have not yet been completely elucidated. The current study investigates whether the VPS26b-associated retromer complex can be used as a neurodegeneration model. Previously, we observed a significant reduction in VPS35 and VPS29 in the brain cells of in VPS26b-deficient mice as well as an absence of the VPS26b-VPS29-VPS35 retromer complex despite the normal presence of VPS26a-VPS29-VPS35. Recent studies have suggested that low levels of VPS35 can lead to Alzheimer's disease-like phenotypes including cognitive memory deficits. In this study, we successfully demonstrate an association between the absence of the VPS26b-VPS29-VPS35 retromer complex, reduced cell density in the CA3 region of the hippocampus, and learning disability in VPS26b knock-out mice. The results also indicate that the VPS26b-associated retromer complex affects neurodegenerative disorders and learning processes.
Keywords
Alzheimer's disease; learning deficits; neurodegeneration; vacuolar protein sorting-associated protein (VPS);
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1 Xia., W. F., Tang, F. L., Xiong, L., Xiong, S., Jung, J. U., Lee, D. H., Li, X. S., Feng, X., Mei, L. and Xiong, W. C. 2013. Vps35 loss promotes hyperresorptive osteoclastogenesis and osteoporosis via sustained RANKL signaling. J. Cell Biol. 200, 821-837.   DOI
2 Lin, T. B, Lai, C. Y., Hsieh, M. C., Wang, H. H., Cheng, J. K., Chau, Y. P., Chen, G. D. and Peng, H. Y. 2015. VPS26ASNX27 Interaction-dependent mGluR5 recycling in dorsal horn neurons mediates neuropathic pain in rats. J. Neurosci. 35, 14943-14955.   DOI
3 Fusea, A., Furuyaa, N., Kakutac, S., Inosea, A., Satoa, M., Koikec, M., Saikia, S. and Hattori, N. 2015. VPS29-VPS35 intermediate of retromer is stable and may be involved in the retromer complex assembly process. FEBS Lett. 589, 1430-1436.   DOI
4 Haft, C. R., de la Luz Sierra, M., Bafford, R., Lesniak., M. A, Barr, V. A. and Taylor, S. I. 2000. Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and 35: assembly into multimeric complexes. Mol. Biol. Cell 11, 4105-4116.   DOI
5 Kerr, M. C., Bennetts, J. S., Simpson, F., Thomas, E. C., Flegg, C., Gleeson, P. A., Wicking, C. and Teasdale, R. D. 2005. A novel mammalian retromer component, Vps26B. Traffic 6, 991-1001.   DOI
6 Lee, J. J., Radice, G., Perkins, C. P. and Costantini, F. 1992. Identification and characterization of a novel, evolutionarily conserved gene disrupted by the murine H beta 58 embryonic lethal transgene insertion. Development 115, 277-288.   DOI
7 Kim, E., Lee, J. W., Baek, D. C., Lee, S. R., Kim, M. S., Kim, S. H., Imakawa, K. and Chang, K. T. 2008. Identification of novel retromer complexes in the mouse testis. Biochem. Biophys. Res. Commun. 375, 16-21.   DOI
8 Kim, E., Lee, Y., Lee, H. J., Kim, J. S., Song, B. S., Huh, J. W., Lee, S. R. Kim, S. U., Kim, S. H., Hong, Y., Shim, I. and Chang, K. T. 2010. Implication of mouse Vps26b-Vps29-Vps35 retromer complex in sortilin trafficking. Biochem. Biophys. Res. Commun. 403, 167-171.   DOI
9 Lane, C. A., Hardy, J. and Schott, J. M. 2018. Alzheimer's disease. Eur. J. Neurol. 25, 59-70.   DOI
10 Muhammad, A., Flores, I., Zhang, H., Yu, R., Staniszewski, A., Planel, E., Herman, M., Ho, L., Kreber, R., Honig, L., Ganetzky, B., Duff, K., Arancio, O. and Small, S. A. 2008. Retromer deficiency observed in Alzheimer's disease causes hippocampal dysfunction, neurodegeneration, and Abeta accumulation. Proc. Natl. Acad. Sci. USA. 105, 7327-7332.   DOI
11 Nykjaer, A., Lee, R., Teng, K. K., Jansen, P., Madsen, P., Nielsen, M. S., Jansen, P. Madsen, P., Nielsen, M. S., Jacobsen, C., Kliemannel, M., Schwarx, E., Willnow, T. E., Hempstead, B. L. and Petersen, C. M. 2004. Sortilin is essential for proNGF-induced neuronal cell death. Nature 427, 843-848.   DOI