Author:
Wu Shuang,Majeed Sophia R.,Evans Timothy M.,Camus Marine D.,Wong Nicole M. L.,Schollmeier Yvette,Park Minjong,Muppidi Jagan R.,Reboldi Andrea,Parham Peter,Cyster Jason G.,Brodsky Frances M.
Abstract
Clathrin, a cytosolic protein composed of heavy and light chain subunits, assembles into a vesicle coat, controlling receptor-mediated endocytosis. To establish clathrin light chain (CLC) function in vivo, we engineered mice lacking CLCa, the major CLC isoform in B lymphocytes, generating animals with CLC-deficient B cells. In CLCa-null mice, the germinal centers have fewer B cells, and they are enriched for IgA-producing cells. This enhanced switch to IgA production in the absence of CLCa was attributable to increased transforming growth factor β receptor 2 (TGFβR2) signaling resulting from defective endocytosis. Internalization of C-X-C chemokine receptor 4 (CXCR4), but not CXCR5, was affected in CLCa-null B cells, and CLC depletion from cell lines affected endocytosis of the δ-opioid receptor, but not the β2-adrenergic receptor, defining a role for CLCs in the uptake of a subset of signaling receptors. This instance of clathrin subunit deletion in vertebrates demonstrates that CLCs contribute to clathrin’s role in vivo by influencing cargo selectivity, a function previously assigned exclusively to adaptor molecules.
Funder
HHS | National Institutes of Health
HHS | NIH | National Cancer Institute
Wellcome Trust
Publisher
Proceedings of the National Academy of Sciences
Cited by
26 articles.
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