Citation
- Authors: Wu, S., Majeed, S. R., Evans, T. M., Camus, M. D., Wong, N. M., Schollmeier, Y., Park, M., Muppidi, J. R., Reboldi, A., Parham, P., Cyster, J. G., Brodsky, F. M.
- Year: 2016
- Journal: Proc Natl Acad Sci U S A 113 9816-21
- Applications: in vitro / DNA, siRNA and DNA cotransfection / jetPRIME
- Cell types:
- Name: HEK-293
Description: Human embryonic kidney Fibroblast
Known as: HEK293, 293 - Name: HEK-293T
Description: Human embryonic kidney Fibroblast
Known as: HEK293T, 293T
- Name: HEK-293
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 beta receptor 2 (TGFbetaR2) 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 delta-opioid receptor, but not the beta2-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.