Implication of mouse Vps26b-Vps29-Vps35 retromer complex in sortilin trafficking |
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Authors: | Kim Ekyune Lee Youngjeon Lee Hyun-Ju Kim Ji Su Song Bong-Seok Huh Jae-Won Lee Sang-Rae Kim Sun-Uk Kim Sang-Hyun Hong Yonggeun Shim Insop Chang Kyu-Tae |
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Institution: | a National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, 685-1 Yangcheong-ri, Ochang-eup, Chung-buk 363-883, Republic of Korea b Department of Rehabilitation Science in Interdisciplinary PhD Program, College of Biomedical Science and Engineering, Inje University, Republic of Korea c Cardiovascular and Metabolic Disease Center, College of Biomedical Science and Engineering, Inje University, Republic of Korea d Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Republic of Korea |
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Abstract: | The retromer complex, which mediates retrograde transport from endosomes to the trans-Golgi network, is a heteropentameric complex that contains a multifunctional cargo recognition heterotrimer consisted of the vacuolar protein sorting (Vps) subunits Vps26, Vps29, and Vps35. In mammals, there are two different isoforms of Vps26, Vps26a and Vps26b, that localize to the endosome, and to the plasma membrane, respectively. To elucidate the biological significance of the Vps26b isoform, we generated Vps26b knockout mice and studied their molecular, histological, and behavioral phenotypes. We found that the loss of Vps26b results in no significant defects in the behavior, body size, and health of the mice. Vps26b-deficient mice showed a severe reduction of Vps35 protein at cellular level and lacked the Vps26b-Vps29-Vps35 retromer complex, despite the normal presence of the Vps26a-Vps29-Vps35 retromer complex. Relatively, the amount of sortilin was increased approximately 20% in the Vps26b-deficient mice, whereas the sorLA was normal. These results suggest that mouse Vps26b-Vps29-Vps35 retromer complex is implicated in the transport of sortilin from endosomes to the trans-Golgi network (TGN). |
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Keywords: | Retromer complex Vacuolar protein sorting 26b (Vps26b) Vps26b-deficient mice Endosomes trans-Golgi network (TGN) |
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