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The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling

MS4A family members differentially regulate the cell cycle, and aberrant, or loss of, expression of MS4A family proteins has been observed in colon and lung cancer. However, the precise functions of MS4A family proteins and their mechanistic interactions remain unsolved. Here we report that MS4A4 fa...

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Autores principales: Cruse, Glenn, Beaven, Michael A., Music, Stephen C., Bradding, Peter, Gilfillan, Alasdair M., Metcalfe, Dean D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436782/
https://www.ncbi.nlm.nih.gov/pubmed/25717186
http://dx.doi.org/10.1091/mbc.E14-07-1221
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author Cruse, Glenn
Beaven, Michael A.
Music, Stephen C.
Bradding, Peter
Gilfillan, Alasdair M.
Metcalfe, Dean D.
author_facet Cruse, Glenn
Beaven, Michael A.
Music, Stephen C.
Bradding, Peter
Gilfillan, Alasdair M.
Metcalfe, Dean D.
author_sort Cruse, Glenn
collection PubMed
description MS4A family members differentially regulate the cell cycle, and aberrant, or loss of, expression of MS4A family proteins has been observed in colon and lung cancer. However, the precise functions of MS4A family proteins and their mechanistic interactions remain unsolved. Here we report that MS4A4 facilitates trafficking of the receptor tyrosine kinase KIT through endocytic recycling rather than degradation pathways by a mechanism that involves recruitment of KIT to caveolin-1–enriched microdomains. Silencing of MS4A4 in human mast cells altered ligand-induced KIT endocytosis pathways and reduced receptor recycling to the cell surface, thus promoting KIT signaling in the endosomes while reducing that in the plasma membrane, as exemplified by Akt and PLCγ1 phosphorylation, respectively. The altered endocytic trafficking of KIT also resulted in an increase in SCF-induced mast cell proliferation and migration, which may reflect altered signaling in these cells. Our data reveal a novel function for MS4A family proteins in regulating trafficking and signaling, which could have implications in both proliferative and immunological diseases.
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spelling pubmed-44367822015-07-16 The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling Cruse, Glenn Beaven, Michael A. Music, Stephen C. Bradding, Peter Gilfillan, Alasdair M. Metcalfe, Dean D. Mol Biol Cell Articles MS4A family members differentially regulate the cell cycle, and aberrant, or loss of, expression of MS4A family proteins has been observed in colon and lung cancer. However, the precise functions of MS4A family proteins and their mechanistic interactions remain unsolved. Here we report that MS4A4 facilitates trafficking of the receptor tyrosine kinase KIT through endocytic recycling rather than degradation pathways by a mechanism that involves recruitment of KIT to caveolin-1–enriched microdomains. Silencing of MS4A4 in human mast cells altered ligand-induced KIT endocytosis pathways and reduced receptor recycling to the cell surface, thus promoting KIT signaling in the endosomes while reducing that in the plasma membrane, as exemplified by Akt and PLCγ1 phosphorylation, respectively. The altered endocytic trafficking of KIT also resulted in an increase in SCF-induced mast cell proliferation and migration, which may reflect altered signaling in these cells. Our data reveal a novel function for MS4A family proteins in regulating trafficking and signaling, which could have implications in both proliferative and immunological diseases. The American Society for Cell Biology 2015-05-01 /pmc/articles/PMC4436782/ /pubmed/25717186 http://dx.doi.org/10.1091/mbc.E14-07-1221 Text en © 2015 Cruse 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
Cruse, Glenn
Beaven, Michael A.
Music, Stephen C.
Bradding, Peter
Gilfillan, Alasdair M.
Metcalfe, Dean D.
The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling
title The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling
title_full The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling
title_fullStr The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling
title_full_unstemmed The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling
title_short The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling
title_sort cd20 homologue ms4a4 directs trafficking of kit toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436782/
https://www.ncbi.nlm.nih.gov/pubmed/25717186
http://dx.doi.org/10.1091/mbc.E14-07-1221
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