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A bipartite sorting signal ensures specificity of retromer complex in membrane protein recycling.

ABSTRACT: 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 F/Y/W. However, this sequence is present in almost all proteins encoded in the genome. Also, several identified recycling sequences do not follow this rule. How then does retromer precisely select its cargos? 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, retromer interacts with cargos in a more complex manner than previously thought, which facilitates precise cargo recognition.

SUBMITTER: Suzuki SW

PROVIDER: S-EPMC6719449 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A bipartite sorting signal ensures specificity of retromer complex in membrane protein recycling.

Suzuki Sho W SW Chuang Ya-Shan YS Li Ming M Seaman Matthew N J MNJ Emr Scott D SD

The Journal of cell biology 20190723 9

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 F/Y/W. However, this sequence is present in almost all proteins encoded in the genome. Also, several identified recycling sequences do not follow this rule. How then does retromer precisely select its cargos? Here, we reveal that an additiona ...[more]

PMID: 31337624

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