CHC22 clathrin recruitment to the early secretory pathway requires two-site interaction with SNX5 and p115
- PMID: 39160272
- PMCID: PMC11445476
- DOI: 10.1038/s44318-024-00198-y
CHC22 clathrin recruitment to the early secretory pathway requires two-site interaction with SNX5 and p115
Abstract
The two clathrin isoforms, CHC17 and CHC22, mediate separate intracellular transport routes. CHC17 performs endocytosis and housekeeping membrane traffic in all cells. CHC22, expressed most highly in skeletal muscle, shuttles the glucose transporter GLUT4 from the ERGIC (endoplasmic-reticulum-to-Golgi intermediate compartment) directly to an intracellular GLUT4 storage compartment (GSC), from where GLUT4 can be mobilized to the plasma membrane by insulin. Here, molecular determinants distinguishing CHC22 from CHC17 trafficking are defined. We show that the C-terminal trimerization domain of CHC22 interacts with SNX5, which also binds the ERGIC tether p115. SNX5, and the functionally redundant SNX6, are required for CHC22 localization independently of their participation in the endosomal ESCPE-1 complex. In tandem, an isoform-specific patch in the CHC22 N-terminal domain separately mediates binding to p115. This dual mode of clathrin recruitment, involving interactions at both N- and C-termini of the heavy chain, is required for CHC22 targeting to ERGIC membranes to mediate the Golgi-bypass route for GLUT4 trafficking. Interference with either interaction inhibits GLUT4 targeting to the GSC, defining a bipartite mechanism regulating a key pathway in human glucose metabolism.
Keywords: CHC22; Clathrin; Golgi bypass; Sorting nexin 5; p115.
© 2024. The Author(s).
Conflict of interest statement
The authors declare no competing interests.
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References
-
- Bogan JS (2012) Regulation of glucose transporter translocation in health and diabetes. Annu Rev Biochem 81:507–532 - PubMed
-
- Bolte S, Cordelieres FP (2006) A guided tour into subcellular colocalization analysis in light microscopy. J Microsc 224:213–232 - PubMed
-
- Briant K, Redlingshöfer L, Brodsky FM (2020) Clathrin’s life beyond 40: connecting biochemistry with physiology and disease. Curr Opin Cell Biol 65:141–149 - PubMed
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