Regulation of clathrin adaptor function in endocytosis: novel role for the SAM domain |
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| Authors: | Santiago M Di Pietro Duilio Cascio Daniel Feliciano James U Bowie Gregory S Payne |
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| Affiliation: | 1. Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO, USA;2. Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, USA;3. Department of Energy Institute of Genomics and Proteomics, University of California at Los Angeles, Los Angeles, CA, USA;4. Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA, USA;5. Department of Biological Chemistry, School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA |
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| Abstract: | During clathrin‐mediated endocytosis, adaptor proteins play central roles in coordinating the assembly of clathrin coats and cargo selection. Here we characterize the binding of the yeast endocytic adaptor Sla1p to clathrin through a variant clathrin‐binding motif that is negatively regulated by the Sla1p SHD2 domain. The crystal structure of SHD2 identifies the domain as a sterile α‐motif (SAM) domain and shows a propensity to oligomerize. By co‐immunoprecipitation, Sla1p binds to clathrin and self‐associates in vivo. Mutations in the clathrin‐binding motif that abolish clathrin binding and structure‐based mutations in SHD2 that impede self‐association result in endocytosis defects and altered dynamics of Sla1p assembly at the sites of endocytosis. These results define a novel mechanism for negative regulation of clathrin binding by an adaptor and suggest a role for SAM domains in clathrin‐mediated endocytosis. |
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| Keywords: | adaptor clathrin endocytosis SAM domain Sla1 |
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