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Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium

Clathrin-mediated endocytosis is a major regulator of cell-surface protein internalization. Clathrin and other proteins assemble into small invaginating structures at the plasma membrane termed clathrin-coated pits (CCPs) that mediate vesicle formation. In addition, epidermal growth factor receptor...

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Autores principales: Delos Santos, Ralph Christian, Bautista, Stephen, Lucarelli, Stefanie, Bone, Leslie N., Dayam, Roya M., Abousawan, John, Botelho, Roberto J., Antonescu, Costin N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638584/
https://www.ncbi.nlm.nih.gov/pubmed/28814502
http://dx.doi.org/10.1091/mbc.E16-12-0871
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author Delos Santos, Ralph Christian
Bautista, Stephen
Lucarelli, Stefanie
Bone, Leslie N.
Dayam, Roya M.
Abousawan, John
Botelho, Roberto J.
Antonescu, Costin N.
author_facet Delos Santos, Ralph Christian
Bautista, Stephen
Lucarelli, Stefanie
Bone, Leslie N.
Dayam, Roya M.
Abousawan, John
Botelho, Roberto J.
Antonescu, Costin N.
author_sort Delos Santos, Ralph Christian
collection PubMed
description Clathrin-mediated endocytosis is a major regulator of cell-surface protein internalization. Clathrin and other proteins assemble into small invaginating structures at the plasma membrane termed clathrin-coated pits (CCPs) that mediate vesicle formation. In addition, epidermal growth factor receptor (EGFR) signaling is regulated by its accumulation within CCPs. Given the diversity of proteins regulated by clathrin-mediated endocytosis, how this process may distinctly regulate specific receptors is a key question. We examined the selective regulation of clathrin-dependent EGFR signaling and endocytosis. We find that perturbations of phospholipase Cγ1 (PLCγ1), Ca(2+), or protein kinase C (PKC) impair clathrin-mediated endocytosis of EGFR, the formation of CCPs harboring EGFR, and EGFR signaling. Each of these manipulations was without effect on the clathrin-mediated endocytosis of transferrin receptor (TfR). EGFR and TfR were recruited to largely distinct clathrin structures. In addition to control of initiation and assembly of CCPs, EGF stimulation also elicited a Ca(2+)- and PKC-dependent reduction in synaptojanin1 recruitment to clathrin structures, indicating broad control of CCP assembly by Ca(2+) signals. Hence EGFR elicits PLCγ1-calcium signals to facilitate formation of a subset of CCPs, thus modulating its own signaling and endocytosis. This provides evidence for the versatility of CCPs to control diverse cellular processes.
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spelling pubmed-56385842017-12-30 Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium Delos Santos, Ralph Christian Bautista, Stephen Lucarelli, Stefanie Bone, Leslie N. Dayam, Roya M. Abousawan, John Botelho, Roberto J. Antonescu, Costin N. Mol Biol Cell Articles Clathrin-mediated endocytosis is a major regulator of cell-surface protein internalization. Clathrin and other proteins assemble into small invaginating structures at the plasma membrane termed clathrin-coated pits (CCPs) that mediate vesicle formation. In addition, epidermal growth factor receptor (EGFR) signaling is regulated by its accumulation within CCPs. Given the diversity of proteins regulated by clathrin-mediated endocytosis, how this process may distinctly regulate specific receptors is a key question. We examined the selective regulation of clathrin-dependent EGFR signaling and endocytosis. We find that perturbations of phospholipase Cγ1 (PLCγ1), Ca(2+), or protein kinase C (PKC) impair clathrin-mediated endocytosis of EGFR, the formation of CCPs harboring EGFR, and EGFR signaling. Each of these manipulations was without effect on the clathrin-mediated endocytosis of transferrin receptor (TfR). EGFR and TfR were recruited to largely distinct clathrin structures. In addition to control of initiation and assembly of CCPs, EGF stimulation also elicited a Ca(2+)- and PKC-dependent reduction in synaptojanin1 recruitment to clathrin structures, indicating broad control of CCP assembly by Ca(2+) signals. Hence EGFR elicits PLCγ1-calcium signals to facilitate formation of a subset of CCPs, thus modulating its own signaling and endocytosis. This provides evidence for the versatility of CCPs to control diverse cellular processes. The American Society for Cell Biology 2017-10-15 /pmc/articles/PMC5638584/ /pubmed/28814502 http://dx.doi.org/10.1091/mbc.E16-12-0871 Text en © 2017 Delos Santos et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Delos Santos, Ralph Christian
Bautista, Stephen
Lucarelli, Stefanie
Bone, Leslie N.
Dayam, Roya M.
Abousawan, John
Botelho, Roberto J.
Antonescu, Costin N.
Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium
title Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium
title_full Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium
title_fullStr Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium
title_full_unstemmed Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium
title_short Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium
title_sort selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase c and calcium
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638584/
https://www.ncbi.nlm.nih.gov/pubmed/28814502
http://dx.doi.org/10.1091/mbc.E16-12-0871
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