RGD Reference Report - Retromer and sorting nexins in endosomal sorting. - Rat Genome Database
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Retromer and sorting nexins in endosomal sorting.

Authors: Gallon, M  Cullen, PJ 
Citation: Gallon M and Cullen PJ, Biochem Soc Trans. 2015 Feb;43(1):33-47. doi: 10.1042/BST20140290.
RGD ID: 10450542
Pubmed: (View Article at PubMed) PMID:25619244
DOI: Full-text: DOI:10.1042/BST20140290

The evolutionarily conserved endosomal retromer complex rescues transmembrane proteins from the lysosomal degradative pathway and facilitates their recycling to other cellular compartments. Retromer functions in conjunction with numerous associated proteins, including select members of the sorting nexin (SNX) family. In the present article, we review the molecular architecture and cellular roles of retromer and its various functional partners. The endosomal network is a crucial hub in the trafficking of proteins through the cellular endomembrane system. Transmembrane proteins, here termed cargos, enter endosomes by endocytosis from the plasma membrane or by trafficking from the trans-Golgi network (TGN). Endosomal cargo proteins face one of the two fates: retention in the endosome, leading ultimately to lysosomal degradation or export from the endosome for reuse ('recycling'). The balance of protein degradation and recycling is crucial to cellular homoeostasis; inappropriate sorting of proteins to either fate leads to cellular dysfunction. Retromer is an endosome-membrane-associated protein complex central to the recycling of many cargo proteins from endosomes, both to the TGN and the plasma membrane (and other specialized compartments, e.g. lysosome-related organelles). Retromer function is reliant on a number of proteins from the SNX family. In the present article, we discuss this inter-relationship and how defects in retromer function are increasingly being linked with human disease.

Annotation

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Ankrd27  (ankyrin repeat domain 27)
Dnajc13  (DnaJ heat shock protein family (Hsp40) member C13)
Ehd1  (EH-domain containing 1)
Snx1  (sorting nexin 1)
Snx2  (sorting nexin 2)
Snx27  (sorting nexin 27)
Snx3  (sorting nexin 3)
Snx5  (sorting nexin 5)
Snx6  (sorting nexin 6)
Tbc1d5  (TBC1 domain family, member 5)
Vps26a  (VPS26 retromer complex component A)
Vps26b  (VPS26 retromer complex component B)
Vps29  (VPS29 retromer complex component)
Vps35  (VPS35 retromer complex component)
Washc1  (WASH complex subunit 1)
Washc2c  (WASH complex subunit 2C)
Washc3  (WASH complex subunit 3)
Washc4  (WASH complex subunit 4)
Washc5  (WASH complex subunit 5)

Genes (Mus musculus)
Ankrd27  (ankyrin repeat domain 27 (VPS9 domain))
Dnajc13  (DnaJ heat shock protein family (Hsp40) member C13)
Ehd1  (EH-domain containing 1)
Snx1  (sorting nexin 1)
Snx2  (sorting nexin 2)
Snx27  (sorting nexin family member 27)
Snx3  (sorting nexin 3)
Snx5  (sorting nexin 5)
Snx6  (sorting nexin 6)
Tbc1d5  (TBC1 domain family, member 5)
Vps26a  (VPS26 retromer complex component A)
Vps26b  (VPS26 retromer complex component B)
Vps29  (VPS29 retromer complex component)
Vps35  (VPS35 retromer complex component)
Washc1  (WASH complex subunit 1)
Washc2  (WASH complex subunit 2`)
Washc3  (WASH complex subunit 3)
Washc4  (WASH complex subunit 4)
Washc5  (WASH complex subunit 5)

Genes (Homo sapiens)
ANKRD27  (ankyrin repeat domain 27)
DNAJC13  (DnaJ heat shock protein family (Hsp40) member C13)
EHD1  (EH domain containing 1)
SNX1  (sorting nexin 1)
SNX2  (sorting nexin 2)
SNX27  (sorting nexin 27)
SNX3  (sorting nexin 3)
SNX5  (sorting nexin 5)
SNX6  (sorting nexin 6)
TBC1D5  (TBC1 domain family member 5)
VPS26A  (VPS26, retromer complex component A)
VPS26B  (VPS26, retromer complex component B)
VPS29  (VPS29 retromer complex component)
VPS35  (VPS35 retromer complex component)
WASHC1  (WASH complex subunit 1)
WASHC2A  (WASH complex subunit 2A)
WASHC3  (WASH complex subunit 3)
WASHC4  (WASH complex subunit 4)
WASHC5  (WASH complex subunit 5)


Additional Information