Implication of mouse Vps26b-Vps29-Vps35 retromer complex in sortilin trafficking.
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).
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, 685-1 Yangcheong-ri, Ochang-eup, Chung-buk 363-883, Republic of Korea.
Ekyune
E
Kim
Youngjeon
Y
Lee
Hyun-Ju
HJ
Lee
Ji Su
JS
Kim
Bong-Seok
BS
Song
Jae-Won
JW
Huh
Sang-Rae
SR
Lee
Sun-Uk
SU
Kim
Sang-Hyun
SH
Kim
Yonggeun
Y
Hong
Insop
I
Shim
Kyu-Tae
KT
Chang
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D055503:Protein Multimerization; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D033921:Vesicular Transport Proteins; D000099183:Sortilin; C503111:VPS29 protein, mouse; C089989:Vps26 protein, mouse; C101274:Vps35 protein, mouse