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The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism

During the development of the peripheral nervous system, the large number of apoptotic neurons generated are phagocytosed by glial precursor cells. This clearance is mediated, in part, through the mammalian engulfment receptor Jedi-1. However, the mechanisms by which Jedi-1 mediates phagocytosis are...

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Autores principales: Sullivan, Chelsea S., Scheib, Jami L., Ma, Zhong, Dang, Rajan P., Schafer, Johanna M., Hickman, Francis E., Brodsky, Frances M., Ravichandran, Kodi S., Carter, Bruce D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055271/
https://www.ncbi.nlm.nih.gov/pubmed/24743597
http://dx.doi.org/10.1091/mbc.E13-11-0658
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author Sullivan, Chelsea S.
Scheib, Jami L.
Ma, Zhong
Dang, Rajan P.
Schafer, Johanna M.
Hickman, Francis E.
Brodsky, Frances M.
Ravichandran, Kodi S.
Carter, Bruce D.
author_facet Sullivan, Chelsea S.
Scheib, Jami L.
Ma, Zhong
Dang, Rajan P.
Schafer, Johanna M.
Hickman, Francis E.
Brodsky, Frances M.
Ravichandran, Kodi S.
Carter, Bruce D.
author_sort Sullivan, Chelsea S.
collection PubMed
description During the development of the peripheral nervous system, the large number of apoptotic neurons generated are phagocytosed by glial precursor cells. This clearance is mediated, in part, through the mammalian engulfment receptor Jedi-1. However, the mechanisms by which Jedi-1 mediates phagocytosis are poorly understood. Here we demonstrate that Jedi-1 associates with GULP, the mammalian homologue of CED-6, an adaptor protein required for phagocytosis mediated by the nematode engulfment receptor CED-1. Silencing GULP or mutating the NPXY motif in Jedi-1, which is required for GULP binding, prevents Jedi-1–mediated phagocytosis. How GULP promotes engulfment is not known. Of interest, we find that Jedi-1–induced phagocytosis requires GULP binding to clathrin heavy chain (CHC). During engulfment, CHC is tyrosine phosphorylated, which is required for Jedi-mediated engulfment. Both phosphoclathrin and actin accumulate around engulfed microspheres. Furthermore, knockdown of CHC in HeLa cells prevents Jedi-1–mediated engulfment of microspheres, and knockdown in glial precursors prevents the engulfment of apoptotic neurons. Taken together, these results reveal that Jedi-1 signals through recruitment of GULP, which promotes phagocytosis through a noncanonical phosphoclathrin-dependent mechanism.
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spelling pubmed-40552712014-08-30 The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism Sullivan, Chelsea S. Scheib, Jami L. Ma, Zhong Dang, Rajan P. Schafer, Johanna M. Hickman, Francis E. Brodsky, Frances M. Ravichandran, Kodi S. Carter, Bruce D. Mol Biol Cell Articles During the development of the peripheral nervous system, the large number of apoptotic neurons generated are phagocytosed by glial precursor cells. This clearance is mediated, in part, through the mammalian engulfment receptor Jedi-1. However, the mechanisms by which Jedi-1 mediates phagocytosis are poorly understood. Here we demonstrate that Jedi-1 associates with GULP, the mammalian homologue of CED-6, an adaptor protein required for phagocytosis mediated by the nematode engulfment receptor CED-1. Silencing GULP or mutating the NPXY motif in Jedi-1, which is required for GULP binding, prevents Jedi-1–mediated phagocytosis. How GULP promotes engulfment is not known. Of interest, we find that Jedi-1–induced phagocytosis requires GULP binding to clathrin heavy chain (CHC). During engulfment, CHC is tyrosine phosphorylated, which is required for Jedi-mediated engulfment. Both phosphoclathrin and actin accumulate around engulfed microspheres. Furthermore, knockdown of CHC in HeLa cells prevents Jedi-1–mediated engulfment of microspheres, and knockdown in glial precursors prevents the engulfment of apoptotic neurons. Taken together, these results reveal that Jedi-1 signals through recruitment of GULP, which promotes phagocytosis through a noncanonical phosphoclathrin-dependent mechanism. The American Society for Cell Biology 2014-06-15 /pmc/articles/PMC4055271/ /pubmed/24743597 http://dx.doi.org/10.1091/mbc.E13-11-0658 Text en © 2014 Sullivan 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 of Cell Biology.
spellingShingle Articles
Sullivan, Chelsea S.
Scheib, Jami L.
Ma, Zhong
Dang, Rajan P.
Schafer, Johanna M.
Hickman, Francis E.
Brodsky, Frances M.
Ravichandran, Kodi S.
Carter, Bruce D.
The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism
title The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism
title_full The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism
title_fullStr The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism
title_full_unstemmed The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism
title_short The adaptor protein GULP promotes Jedi-1–mediated phagocytosis through a clathrin-dependent mechanism
title_sort adaptor protein gulp promotes jedi-1–mediated phagocytosis through a clathrin-dependent mechanism
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055271/
https://www.ncbi.nlm.nih.gov/pubmed/24743597
http://dx.doi.org/10.1091/mbc.E13-11-0658
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