Proteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis

Abstract Endosomal trafficking of cell surface receptors is essential to their function. Integrins are transmembrane receptors that integrate adhesion to the extracellular matrix with engagement of the cytoskeleton. Ligated integrins mediate diverse signals that regulate matrix assembly, cell surviv...

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Autores principales:	Maisel J. Caliva, Won Seok Yang, Shirley Young-Robbins, Ming Zhou, Hana Yoon, Michelle L. Matter, Mark L. Grimes, Thomas Conrads, Joe William Ramos
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de03163bffee45e4a081229dd13ce7cd
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spelling	oai:doaj.org-article:de03163bffee45e4a081229dd13ce7cd2021-12-02T17:13:17ZProteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis10.1038/s41598-021-99348-z2045-2322https://doaj.org/article/de03163bffee45e4a081229dd13ce7cd2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99348-zhttps://doaj.org/toc/2045-2322Abstract Endosomal trafficking of cell surface receptors is essential to their function. Integrins are transmembrane receptors that integrate adhesion to the extracellular matrix with engagement of the cytoskeleton. Ligated integrins mediate diverse signals that regulate matrix assembly, cell survival, cell morphology, and cell motility. Endosomal trafficking of integrins modulates these signals and contributes to cell motility and is required for cancer cell invasion. The phosphoprotein PEA-15 modulates integrin activation and ERK MAP Kinase signaling. To elucidate novel PEA-15 functions we utilized an unbiased proteomics approach. We identified several binding partners for PEA-15 in the endosome including clathrin and AP-2 as well as integrin β1 and other focal adhesion complex proteins. We confirmed these interactions using proximity ligation analysis, immunofluorescence imaging, pull-down and co-immunoprecipitation. We further found that PEA-15 is enriched in endosomes and was required for efficient endosomal internalization of α5β1 integrin and cellular migration. Importantly, PEA-15 promotion of migration was dependent on PEA-15 phosphorylation at serines 104 and 116. These data support a novel endosomal role for PEA-15 in control of endosomal trafficking of integrins through an association with the β1 integrin and clathrin complexes, and thereby regulation of cell motility.Maisel J. CalivaWon Seok YangShirley Young-RobbinsMing ZhouHana YoonMichelle L. MatterMark L. GrimesThomas ConradsJoe William RamosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maisel J. Caliva Won Seok Yang Shirley Young-Robbins Ming Zhou Hana Yoon Michelle L. Matter Mark L. Grimes Thomas Conrads Joe William Ramos Proteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis
description	Abstract Endosomal trafficking of cell surface receptors is essential to their function. Integrins are transmembrane receptors that integrate adhesion to the extracellular matrix with engagement of the cytoskeleton. Ligated integrins mediate diverse signals that regulate matrix assembly, cell survival, cell morphology, and cell motility. Endosomal trafficking of integrins modulates these signals and contributes to cell motility and is required for cancer cell invasion. The phosphoprotein PEA-15 modulates integrin activation and ERK MAP Kinase signaling. To elucidate novel PEA-15 functions we utilized an unbiased proteomics approach. We identified several binding partners for PEA-15 in the endosome including clathrin and AP-2 as well as integrin β1 and other focal adhesion complex proteins. We confirmed these interactions using proximity ligation analysis, immunofluorescence imaging, pull-down and co-immunoprecipitation. We further found that PEA-15 is enriched in endosomes and was required for efficient endosomal internalization of α5β1 integrin and cellular migration. Importantly, PEA-15 promotion of migration was dependent on PEA-15 phosphorylation at serines 104 and 116. These data support a novel endosomal role for PEA-15 in control of endosomal trafficking of integrins through an association with the β1 integrin and clathrin complexes, and thereby regulation of cell motility.
format	article
author	Maisel J. Caliva Won Seok Yang Shirley Young-Robbins Ming Zhou Hana Yoon Michelle L. Matter Mark L. Grimes Thomas Conrads Joe William Ramos
author_facet	Maisel J. Caliva Won Seok Yang Shirley Young-Robbins Ming Zhou Hana Yoon Michelle L. Matter Mark L. Grimes Thomas Conrads Joe William Ramos
author_sort	Maisel J. Caliva
title	Proteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis
title_short	Proteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis
title_full	Proteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis
title_fullStr	Proteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis
title_full_unstemmed	Proteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis
title_sort	proteomics analysis identifies pea-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/de03163bffee45e4a081229dd13ce7cd
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Proteomics analysis identifies PEA-15 as an endosomal phosphoprotein that regulates α5β1 integrin endocytosis

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