Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.

<h4>Background</h4>The multifunctional receptor LRP1 has been shown to bind and internalize a large number of protein ligands with biological importance such as the pan-protease inhibitor alpha2-macroglobulin (alpha2M). We recently identified Alpha2ML1, a new member of the alpha2M gene f...

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Autores principales:	Marie-Florence Galliano, Eve Toulza, Nathalie Jonca, Steven L Gonias, Guy Serre, Marina Guerrin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c58a53838a14bd6926d226fc47ec1e6
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spelling	oai:doaj.org-article:9c58a53838a14bd6926d226fc47ec1e62021-11-25T06:11:28ZBinding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.1932-620310.1371/journal.pone.0002729https://doaj.org/article/9c58a53838a14bd6926d226fc47ec1e62008-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18648652/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The multifunctional receptor LRP1 has been shown to bind and internalize a large number of protein ligands with biological importance such as the pan-protease inhibitor alpha2-macroglobulin (alpha2M). We recently identified Alpha2ML1, a new member of the alpha2M gene family, expressed in epidermis. alpha2ML1 might contribute to the regulation of desquamation through its inhibitory activity towards proteases of the chymotrypsin family, notably KLK7. The expression of LRP1 in epidermis as well as its ability to internalize alpha2ML1 was investigated.<h4>Methods and principal findings</h4>In human epidermis, LRP1 is mainly expressed within the granular layer of the epidermis, which gathers the most differentiated keratinocytes, as shown by immunohistochemistry and immunofluorescence using two different antibodies. By using various experimental approaches, we show that the receptor binding domain of alpha2ML1 (RBDl) is specifically internalized into the macrophage-like cell line RAW and colocalizes with LRP1 upon internalization. Coimmunoprecipitation assays demonstrate that RBDl binds LRP1 at the cell surface. Addition of RAP, a universal inhibitor of ligand binding to LRP1, prevents RBDl binding at the cell surface as well as internalization into RAW cells. Silencing Lrp1 expression with specific siRNA strongly reduces RBDl internalization.<h4>Conclusions and significance</h4>Keratinocytes of the upper differentiated layers of epidermis express LRP1 as well as alpha2ML1. Our study also reveals that alpha2ML1 is a new ligand for LRP1. Our findings are consistent with endocytosis by LRP1 of complexes formed between alpha2ML1 and proteases. LRP1 may thus control desquamation by regulating the biodisponibility of extracellular proteases.Marie-Florence GallianoEve ToulzaNathalie JoncaSteven L GoniasGuy SerreMarina GuerrinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 7, p e2729 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marie-Florence Galliano Eve Toulza Nathalie Jonca Steven L Gonias Guy Serre Marina Guerrin Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.
description	<h4>Background</h4>The multifunctional receptor LRP1 has been shown to bind and internalize a large number of protein ligands with biological importance such as the pan-protease inhibitor alpha2-macroglobulin (alpha2M). We recently identified Alpha2ML1, a new member of the alpha2M gene family, expressed in epidermis. alpha2ML1 might contribute to the regulation of desquamation through its inhibitory activity towards proteases of the chymotrypsin family, notably KLK7. The expression of LRP1 in epidermis as well as its ability to internalize alpha2ML1 was investigated.<h4>Methods and principal findings</h4>In human epidermis, LRP1 is mainly expressed within the granular layer of the epidermis, which gathers the most differentiated keratinocytes, as shown by immunohistochemistry and immunofluorescence using two different antibodies. By using various experimental approaches, we show that the receptor binding domain of alpha2ML1 (RBDl) is specifically internalized into the macrophage-like cell line RAW and colocalizes with LRP1 upon internalization. Coimmunoprecipitation assays demonstrate that RBDl binds LRP1 at the cell surface. Addition of RAP, a universal inhibitor of ligand binding to LRP1, prevents RBDl binding at the cell surface as well as internalization into RAW cells. Silencing Lrp1 expression with specific siRNA strongly reduces RBDl internalization.<h4>Conclusions and significance</h4>Keratinocytes of the upper differentiated layers of epidermis express LRP1 as well as alpha2ML1. Our study also reveals that alpha2ML1 is a new ligand for LRP1. Our findings are consistent with endocytosis by LRP1 of complexes formed between alpha2ML1 and proteases. LRP1 may thus control desquamation by regulating the biodisponibility of extracellular proteases.
format	article
author	Marie-Florence Galliano Eve Toulza Nathalie Jonca Steven L Gonias Guy Serre Marina Guerrin
author_facet	Marie-Florence Galliano Eve Toulza Nathalie Jonca Steven L Gonias Guy Serre Marina Guerrin
author_sort	Marie-Florence Galliano
title	Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.
title_short	Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.
title_full	Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.
title_fullStr	Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.
title_full_unstemmed	Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.
title_sort	binding of alpha2ml1 to the low density lipoprotein receptor-related protein 1 (lrp1) reveals a new role for lrp1 in the human epidermis.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/9c58a53838a14bd6926d226fc47ec1e6
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Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermis.

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