Mammalian VPS45 orchestrates trafficking through the endosomal system

被引：19

作者：

Frey, Laura ^{[1
]}

Zietara, Natalia ^{[1
]}

Lyszkiewicz, Marcin ^{[1
]}

Marquardt, Benjamin ^{[1
]}

Mizoguchi, Yoko ^{[1
]}

Linder, Monika, I ^{[1
]}

Liu, Yanshan ^{[1
]}

Giesert, Florian ^{[2
]}

Wurst, Wolfgang ^{[2
]}

Dahlhoff, Maik ^{[3
]}

Schneider, Marlon R. ^{[3
]}

Wolf, Eckhard ^{[3
]}

Somech, Raz ^{[4
]}

Klein, Christoph ^{[1
]}

机构：

[1] Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Dept Pediat, Lindwurmstr 4, D-803377 Munich, Germany

[2] German Res Ctr Environm Hlth GmbH, Inst Dev Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany

[3] Ludwig Maximilians Univ Munchen, Gene Ctr, Inst Mol Anim Breeding & Biotechnol, Munich, Germany

[4] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr,Immunol Serv,Jeffrey Modell Fdn Ctr, Edmond & Lily Safra Childrens Hosp,Pediat Dept A, Tel Aviv, Israel

来源：

BLOOD | 2021年 / 137卷 / 14期

关键词：

ENDOCYTIC TRAFFICKING; RABENOSYN-5; RAB5; TRANSPORT; PROTEINS; GENE; COMPARTMENT; BIOGENESIS; MUTATIONS; EFFECTORS;

D O I：

10.1182/blood.2020006871

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Vacuolar protein sorting 45 homolog (VPS45), a member of the Sec1/Munc18 (SM) family, has been implicated in the regulation of endosomal trafficking. VPS45 deficiency in human patients results in congenital neutropenia, bone marrow fibrosis, and extramedullary renal hematopoiesis. Detailed mechanisms of the VPS45 function are unknown. Here, we show an essential role of mammalian VPS45 in maintaining the intracellular organization of endolysosomal vesicles and promoting recycling of cell-surface receptors. Loss of VPS45 causes defective Rab5-to-Rab7 conversion resulting in trapping of cargos in early endosomes and impaired delivery to lysosomes. In this context, we demonstrate aberrant trafficking of the granulocyte colony-stimulating factor receptor in the absence of VPS45. Furthermore, we find that lack of VPS45 in mice is not compatible with embryonic development. Thus, we identify mammalian VPS45 as a critical regulator of trafficking through the endosomal system and early embryogenesis of mice.

引用

页码：1932 / 1944

页数：13

共 53 条

[11] The SM protein VPS-45 is required for RAB-5-dependent endocytic transport in Caenorhabditis elegans [J].