Wu, S;
Majeed, SR;
Evans, TM;
Camus, MD;
Wong, NML;
Schollmeier, Y;
Park, M;
... Brodsky, FM; + view all
(2016)
Clathrin light chains' role in selective endocytosis influences antibody isotype switching.
PNAS - Proceedings of The National Academy of Sciences of The United States of America
, 113
(35)
pp. 9816-9821.
10.1073/pnas.1611189113.
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Wu et al PNAS approved version.pdf - Accepted Version Download (13MB) | Preview |
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.
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