Identification of a conserved motif required for Vps35p/Vps26p interaction and assembly of the retromer complex.
The retromer complex is a conserved cytoplasmic coat complex that mediates the endosome-to-Golgi retrieval of vacuole/lysosome hydrolase receptors in yeast and mammals. The recognition of cargo proteins by the retromer is performed by the Vps35p/VPS35 (where Vps is vacuolar protein sorting) component, which together with Vps26p/VPS26 and Vps29p/VPS29, forms the cargo-selective subcomplex. In this report, we have identified a highly-conserved region of Vps35p/VPS35 that is essential for the interaction with Vps26p/VPS26 and for assembly of the retromer complex. Mutation of residues within the conserved region results in Vps35p/VPS35 mutants, which cannot bind to Vps26p/VPS26 and are not efficiently targeted to the endosomal membrane. These data implicate Vps26p/VPS26 in regulating Vps35p/VPS35 membrane association and therefore suggest a role for Vps26p/VPS26 in cargo recognition.
Gokool
Suzanne
S
University of Cambridge, Cambridge Institute for Medical Research/Department of Clinical Biochemistry, Wellcome Trust/MRC building, Addenbrookes Hospital, Cambridge CB2 0XY, UK.
Tattersall
Daniel
D
Reddy
Jonathan V
JV
Seaman
Matthew N J
MN
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D003593:Cytoplasm / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D021381:Protein Transport / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D033921:Vesicular Transport Proteins; C089989:Vps26 protein, mouse; C101274:Vps35 protein, mouse
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