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- Title
Mechanism of cargo recognition by retromer-linked SNX-BAR proteins.
- Authors
Yong, Xin; Zhao, Lin; Deng, Wankun; Sun, Hongbin; Zhou, Xue; Mao, Lejiao; Hu, Wenfeng; Shen, Xiaofei; Sun, Qingxiang; Billadeau, Daniel D.; Xue, Yu; Jia, Da
- Abstract
Endocytic recycling of internalized transmembrane proteins is essential for many important physiological processes. Recent studies have revealed that retromer-related Sorting Nexin family (SNX)–Bin/Amphiphysin/Rvs (BAR) proteins can directly recognize cargoes like cation-independent mannose 6-phosphate receptor (CI-MPR) and Insulin-like growth factor 1 receptor (IGF1R); however, it remains poorly understood how SNX-BARs select specific cargo proteins and whether they recognize additional ligands. Here, we discovered that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) domain of SNX5 or SNX6 and a bipartite motif, termed SNX-BAR-binding motif (SBM), in the cargoes. Using this motif, we identified over 70 putative SNX-BAR ligands, many of which play critical roles in apoptosis, cell adhesion, signal transduction, or metabolite homeostasis. Remarkably, SNX-BARs could cooperate with both SNX27 and retromer in the recycling of ligands encompassing the SBM, PDZ-binding motif, or both motifs. Overall, our studies establish that SNX-BARs function as a direct cargo-selecting module for a large set of transmembrane proteins transiting the endosome, in addition to their roles in phospholipid recognition and biogenesis of tubular structures. Internalized transmembrane proteins can be recognized by specific protein complexes and diverted away from the degradation process. This study identifies a new sorting motif recognized by retromer-linked SNX-BAR proteins and reveals a large repertoire of potential cargoes recycled by the SNX-BAR proteins.
- Subjects
INSULIN-like growth factor receptors; SOMATOMEDIN C; MEMBRANE proteins; ENDOCYTOSIS; PROTEINS
- Publication
PLoS Biology, 2020, Vol 18, Issue 3, p1
- ISSN
1544-9173
- Publication type
Article
- DOI
10.1371/journal.pbio.3000631