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Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages
The Fcγ receptor (FcγR)-mediated phagocytosis of macrophages is a complex process where remodeling of both the actin-based cytoskeleton and plasma membrane occur coordinately. Several different families of small GTPases are involved. We have isolated a GTPase-activating protein (GAP) for ADP-ribosyl...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2001
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193405/ https://www.ncbi.nlm.nih.gov/pubmed/11304556 |
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author | Uchida, Hiroshi Kondo, Akiko Yoshimura, Yasunori Mazaki, Yuichi Sabe, Hisataka |
author_facet | Uchida, Hiroshi Kondo, Akiko Yoshimura, Yasunori Mazaki, Yuichi Sabe, Hisataka |
author_sort | Uchida, Hiroshi |
collection | PubMed |
description | The Fcγ receptor (FcγR)-mediated phagocytosis of macrophages is a complex process where remodeling of both the actin-based cytoskeleton and plasma membrane occur coordinately. Several different families of small GTPases are involved. We have isolated a GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF), paxillin-associated protein with ARFGAP activity (PAG)3/Papα/KIAA0400, from mature monocytes and macrophage-like cells. Mammalian ARFs fall into three classes, and the class III isoform (ARF6) has been shown to be involved in FcγR-mediated phagocytosis. Here we report that PAG3 is enriched together with ARF6 and F-actin at phagocytic cups formed beneath immunoglobulin G–opsonized beads in P388D1 macrophages, in which overexpression of ARF6, but not ARF1 (class I) or ARF5 (class II), inhibits the phagocytosis. Overexpression of PAG3, but not its GAP-inactive mutant, attenuated the focal accumulation of F-actin and blocked phagocytosis, although surface levels of the FcγRs were not affected. Other ubiquitously expressed ARFGAPs, G protein–coupled receptor kinase interactors GIT2 and GIT2-short/KIAA0148, which we have shown to exhibit GAP activity for ARF1 in COS-7 cells, did not accumulate at the phagocytic cups or inhibit phagocytosis. Moreover, cooverexpression of ARF6, but not ARF1 or ARF5, restored the phagocytic activity of PAG3-overexpressing cells. We propose that PAG3 acts as a GAP for ARF6 and is hence involved in FcγR-mediated phagocytosis in mouse macrophages. |
format | Text |
id | pubmed-2193405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21934052008-04-14 Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages Uchida, Hiroshi Kondo, Akiko Yoshimura, Yasunori Mazaki, Yuichi Sabe, Hisataka J Exp Med Original Article The Fcγ receptor (FcγR)-mediated phagocytosis of macrophages is a complex process where remodeling of both the actin-based cytoskeleton and plasma membrane occur coordinately. Several different families of small GTPases are involved. We have isolated a GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF), paxillin-associated protein with ARFGAP activity (PAG)3/Papα/KIAA0400, from mature monocytes and macrophage-like cells. Mammalian ARFs fall into three classes, and the class III isoform (ARF6) has been shown to be involved in FcγR-mediated phagocytosis. Here we report that PAG3 is enriched together with ARF6 and F-actin at phagocytic cups formed beneath immunoglobulin G–opsonized beads in P388D1 macrophages, in which overexpression of ARF6, but not ARF1 (class I) or ARF5 (class II), inhibits the phagocytosis. Overexpression of PAG3, but not its GAP-inactive mutant, attenuated the focal accumulation of F-actin and blocked phagocytosis, although surface levels of the FcγRs were not affected. Other ubiquitously expressed ARFGAPs, G protein–coupled receptor kinase interactors GIT2 and GIT2-short/KIAA0148, which we have shown to exhibit GAP activity for ARF1 in COS-7 cells, did not accumulate at the phagocytic cups or inhibit phagocytosis. Moreover, cooverexpression of ARF6, but not ARF1 or ARF5, restored the phagocytic activity of PAG3-overexpressing cells. We propose that PAG3 acts as a GAP for ARF6 and is hence involved in FcγR-mediated phagocytosis in mouse macrophages. The Rockefeller University Press 2001-04-16 /pmc/articles/PMC2193405/ /pubmed/11304556 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Uchida, Hiroshi Kondo, Akiko Yoshimura, Yasunori Mazaki, Yuichi Sabe, Hisataka Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages |
title | Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages |
title_full | Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages |
title_fullStr | Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages |
title_full_unstemmed | Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages |
title_short | Pag3/Papα/Kiaa0400, a Gtpase-Activating Protein for Adp-Ribosylation Factor (Arf), Regulates Arf6 in Fcγ Receptor–Mediated Phagocytosis of Macrophages |
title_sort | pag3/papα/kiaa0400, a gtpase-activating protein for adp-ribosylation factor (arf), regulates arf6 in fcγ receptor–mediated phagocytosis of macrophages |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193405/ https://www.ncbi.nlm.nih.gov/pubmed/11304556 |
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