A Bipartite Sorting Signal Ensures Specificity of Retromer Complex in Membrane Protein Recycling
In the endosomal network, membrane proteins are either sorted into intraluminal vesicles for the lysosomal degradative pathway or exported from the endosome to the trans-Golgi network (TGN) via retrograde transport. Retromer is an evolutionarily conserved protein complex, which sorts functionally diverse membrane proteins into recycling tubules/vesicles from the endosome. Many of the identified cargos possess a recycling signal sequence defined as ØX[L/M/V], where Ø is a bulky aromatic residue and X could be any residue. However, this sequence is present in almost all proteins encoded in the genome. Also, several identified recycling sequences do not follow this rule. How retromer precisely selects its cargos remains unclear. Here, we reveal that an additional motif is also required for cargo retrieval. The two distinct motifs form a bipartite recycling signal recognized by the retromer subunits, Vps26 and Vps35. Strikingly, Vps26 utilizes different binding sites depending on the cargo, allowing retromer to recycle different membrane proteins. Thus, the complicated interaction between the retromer complex and cargoes increases the diversity and specificity in the recognition of cargo recycling.
recycling; Rsp5; Cellular biology; Molecular biology; CPY; Ear1; retromer; Vps10
Emr, Scott David
Lee, Siu Sylvia; Brown, William J.
Biochemistry, Molecular and Cell Biology
Ph.D., Biochemistry, Molecular and Cell Biology
Doctor of Philosophy
dissertation or thesis