Intracellular Localization and Constitutive Endocytosis of CXCR4 in Human CD34+ Hematopoietic Progenitor Cells
CXCR4, the stromal cell–derived factor‐1 receptor, plays an important role in the migration of hematopoietic progenitor/stem cells. The surface and cytoplasmic expression of CXCR4 on human hematopoietic CD34+ cells was investigated. We show that its surface expression is low, whereas a large part of...
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Veröffentlicht in: | Stem cells (Dayton, Ohio) Ohio), 2004-01, Vol.22 (6), p.1015-1029 |
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description | CXCR4, the stromal cell–derived factor‐1 receptor, plays an important role in the migration of hematopoietic progenitor/stem cells. The surface and cytoplasmic expression of CXCR4 on human hematopoietic CD34+ cells was investigated. We show that its surface expression is low, whereas a large part of CXCR4 protein is sequestered intracellularly. Using confocal microscopy, we demonstrated that CXCR4 is colocalized with EEA‐1, Rab5, Rab4, and Rab11, which are localized in early and recycling endosomes. No significant colocalization of CXCR4 with lysosomal markers CD63 and Lamp‐1 was detected. Using antibody feeding experiments, we report a role for CXCR4 constitutive endocytosis in subcellular localization in stably transduced UT7‐CXCR4‐GFP and CD34+ cells. Agonist‐independent endocytosis of CXCR4 occurs through clathrin‐coated vesicles. These data implicate a constitutive endocytosis in the regulation of CXCR4 membrane expression and suggest that constitutive endocytosis may be involved in the regulation of trafficking the human hematopoietic progenitor/stem cells to and in the bone marrow microenvironment. |
doi_str_mv | 10.1634/stemcells.22-6-1015 |
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The surface and cytoplasmic expression of CXCR4 on human hematopoietic CD34+ cells was investigated. We show that its surface expression is low, whereas a large part of CXCR4 protein is sequestered intracellularly. Using confocal microscopy, we demonstrated that CXCR4 is colocalized with EEA‐1, Rab5, Rab4, and Rab11, which are localized in early and recycling endosomes. No significant colocalization of CXCR4 with lysosomal markers CD63 and Lamp‐1 was detected. Using antibody feeding experiments, we report a role for CXCR4 constitutive endocytosis in subcellular localization in stably transduced UT7‐CXCR4‐GFP and CD34+ cells. Agonist‐independent endocytosis of CXCR4 occurs through clathrin‐coated vesicles. These data implicate a constitutive endocytosis in the regulation of CXCR4 membrane expression and suggest that constitutive endocytosis may be involved in the regulation of trafficking the human hematopoietic progenitor/stem cells to and in the bone marrow microenvironment.</description><identifier>ISSN: 1066-5099</identifier><identifier>EISSN: 1549-4918</identifier><identifier>DOI: 10.1634/stemcells.22-6-1015</identifier><identifier>PMID: 15536192</identifier><language>eng</language><publisher>Bristol: John Wiley & Sons, Ltd</publisher><subject>Antigens, CD - biosynthesis ; Antigens, CD34 - biosynthesis ; CD34+ cells ; Cell Membrane - metabolism ; Cell migration ; Cell Movement ; Chemotaxis ; Clathrin - metabolism ; CXCR4 receptor ; Endocytosis ; Flow Cytometry ; Gene Expression Regulation ; Green Fluorescent Proteins - metabolism ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - metabolism ; Humans ; Ligands ; Lysosomal Membrane Proteins ; Membrane Proteins - biosynthesis ; Microscopy, Confocal ; Plasmids - metabolism ; Platelet Membrane Glycoproteins - biosynthesis ; rab GTP-Binding Proteins - biosynthesis ; rab4 GTP-Binding Proteins - biosynthesis ; rab5 GTP-Binding Proteins - biosynthesis ; Receptors, CXCR4 - biosynthesis ; Retroviridae - genetics ; SDF‐1 ; Signal Transduction ; Temperature ; Tetraspanin 30 ; Vesicular Transport Proteins</subject><ispartof>Stem cells (Dayton, Ohio), 2004-01, Vol.22 (6), p.1015-1029</ispartof><rights>Copyright © 2004 AlphaMed Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4645-fd9730939759eceef8d0846811107614c3cd4efbf573d864af8b6d3f5ce420903</citedby><cites>FETCH-LOGICAL-c4645-fd9730939759eceef8d0846811107614c3cd4efbf573d864af8b6d3f5ce420903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15536192$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yanyan</creatorcontrib><creatorcontrib>Foudi, Adlen</creatorcontrib><creatorcontrib>Geay, Jean‐François</creatorcontrib><creatorcontrib>Berthebaud, Magali</creatorcontrib><creatorcontrib>Buet, Dorothée</creatorcontrib><creatorcontrib>Jarrier, Peggy</creatorcontrib><creatorcontrib>Jalil, Abdelali</creatorcontrib><creatorcontrib>Vainchenker, William</creatorcontrib><creatorcontrib>Louache, Fawzia</creatorcontrib><title>Intracellular Localization and Constitutive Endocytosis of CXCR4 in Human CD34+ Hematopoietic Progenitor Cells</title><title>Stem cells (Dayton, Ohio)</title><addtitle>Stem Cells</addtitle><description>CXCR4, the stromal cell–derived factor‐1 receptor, plays an important role in the migration of hematopoietic progenitor/stem cells. The surface and cytoplasmic expression of CXCR4 on human hematopoietic CD34+ cells was investigated. We show that its surface expression is low, whereas a large part of CXCR4 protein is sequestered intracellularly. Using confocal microscopy, we demonstrated that CXCR4 is colocalized with EEA‐1, Rab5, Rab4, and Rab11, which are localized in early and recycling endosomes. No significant colocalization of CXCR4 with lysosomal markers CD63 and Lamp‐1 was detected. Using antibody feeding experiments, we report a role for CXCR4 constitutive endocytosis in subcellular localization in stably transduced UT7‐CXCR4‐GFP and CD34+ cells. Agonist‐independent endocytosis of CXCR4 occurs through clathrin‐coated vesicles. These data implicate a constitutive endocytosis in the regulation of CXCR4 membrane expression and suggest that constitutive endocytosis may be involved in the regulation of trafficking the human hematopoietic progenitor/stem cells to and in the bone marrow microenvironment.</description><subject>Antigens, CD - biosynthesis</subject><subject>Antigens, CD34 - biosynthesis</subject><subject>CD34+ cells</subject><subject>Cell Membrane - metabolism</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Chemotaxis</subject><subject>Clathrin - metabolism</subject><subject>CXCR4 receptor</subject><subject>Endocytosis</subject><subject>Flow Cytometry</subject><subject>Gene Expression Regulation</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Ligands</subject><subject>Lysosomal Membrane Proteins</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Microscopy, Confocal</subject><subject>Plasmids - metabolism</subject><subject>Platelet Membrane Glycoproteins - biosynthesis</subject><subject>rab GTP-Binding Proteins - biosynthesis</subject><subject>rab4 GTP-Binding Proteins - biosynthesis</subject><subject>rab5 GTP-Binding Proteins - biosynthesis</subject><subject>Receptors, CXCR4 - biosynthesis</subject><subject>Retroviridae - genetics</subject><subject>SDF‐1</subject><subject>Signal Transduction</subject><subject>Temperature</subject><subject>Tetraspanin 30</subject><subject>Vesicular Transport Proteins</subject><issn>1066-5099</issn><issn>1549-4918</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1v1DAQhi0EoqXwCyohn7hUKXb8kVg9oXRhK23VqhSJm-V1xpVRYm9tp9Xy69mwK3rlNHN43kczL0KnlJxTyfjnXGC0MAz5vK4rWVFCxSt0TAVXFVe0fb3biZSVIEodoXc5_yKEctG2b9ERFYJJqupjFK5CSWbWTINJeBWtGfxvU3wM2IQedzHk4stU_BPgReij3ZaYfcbR4e5nd8exD3g5jSbg7pLxM7yE0ZS4iR6Kt_g2xQcIvsSEu_nU9-iNM0OGD4d5gn58Xdx3y2p18-2q-7KqLJdcVK5XDSOKqUYosACu7UnLZUspJY2k3DLbc3BrJxrWt5Ib165lz5ywwGuiCDtBn_beTYqPE-SiR5_nL02AOGUtGyK5EnIHsj1oU8w5gdOb5EeTtpoSPdes_9Ws61pLPde8S3086Kf1CP1L5tDrDrjYA89-gO3_OPX3-8V1Xf_V_wFxNo8W</recordid><startdate>20040101</startdate><enddate>20040101</enddate><creator>Zhang, Yanyan</creator><creator>Foudi, Adlen</creator><creator>Geay, Jean‐François</creator><creator>Berthebaud, Magali</creator><creator>Buet, Dorothée</creator><creator>Jarrier, Peggy</creator><creator>Jalil, Abdelali</creator><creator>Vainchenker, William</creator><creator>Louache, Fawzia</creator><general>John Wiley & Sons, Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040101</creationdate><title>Intracellular Localization and Constitutive Endocytosis of CXCR4 in Human CD34+ Hematopoietic Progenitor Cells</title><author>Zhang, Yanyan ; Foudi, Adlen ; Geay, Jean‐François ; Berthebaud, Magali ; Buet, Dorothée ; Jarrier, Peggy ; Jalil, Abdelali ; Vainchenker, William ; Louache, Fawzia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4645-fd9730939759eceef8d0846811107614c3cd4efbf573d864af8b6d3f5ce420903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antigens, CD - biosynthesis</topic><topic>Antigens, CD34 - biosynthesis</topic><topic>CD34+ cells</topic><topic>Cell Membrane - metabolism</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Chemotaxis</topic><topic>Clathrin - metabolism</topic><topic>CXCR4 receptor</topic><topic>Endocytosis</topic><topic>Flow Cytometry</topic><topic>Gene Expression Regulation</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Ligands</topic><topic>Lysosomal Membrane Proteins</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Microscopy, Confocal</topic><topic>Plasmids - metabolism</topic><topic>Platelet Membrane Glycoproteins - biosynthesis</topic><topic>rab GTP-Binding Proteins - biosynthesis</topic><topic>rab4 GTP-Binding Proteins - biosynthesis</topic><topic>rab5 GTP-Binding Proteins - biosynthesis</topic><topic>Receptors, CXCR4 - biosynthesis</topic><topic>Retroviridae - genetics</topic><topic>SDF‐1</topic><topic>Signal Transduction</topic><topic>Temperature</topic><topic>Tetraspanin 30</topic><topic>Vesicular Transport Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Yanyan</creatorcontrib><creatorcontrib>Foudi, Adlen</creatorcontrib><creatorcontrib>Geay, Jean‐François</creatorcontrib><creatorcontrib>Berthebaud, Magali</creatorcontrib><creatorcontrib>Buet, Dorothée</creatorcontrib><creatorcontrib>Jarrier, Peggy</creatorcontrib><creatorcontrib>Jalil, Abdelali</creatorcontrib><creatorcontrib>Vainchenker, William</creatorcontrib><creatorcontrib>Louache, Fawzia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Stem cells (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Yanyan</au><au>Foudi, Adlen</au><au>Geay, Jean‐François</au><au>Berthebaud, Magali</au><au>Buet, Dorothée</au><au>Jarrier, Peggy</au><au>Jalil, Abdelali</au><au>Vainchenker, William</au><au>Louache, Fawzia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intracellular Localization and Constitutive Endocytosis of CXCR4 in Human CD34+ Hematopoietic Progenitor Cells</atitle><jtitle>Stem cells (Dayton, Ohio)</jtitle><addtitle>Stem Cells</addtitle><date>2004-01-01</date><risdate>2004</risdate><volume>22</volume><issue>6</issue><spage>1015</spage><epage>1029</epage><pages>1015-1029</pages><issn>1066-5099</issn><eissn>1549-4918</eissn><abstract>CXCR4, the stromal cell–derived factor‐1 receptor, plays an important role in the migration of hematopoietic progenitor/stem cells. The surface and cytoplasmic expression of CXCR4 on human hematopoietic CD34+ cells was investigated. We show that its surface expression is low, whereas a large part of CXCR4 protein is sequestered intracellularly. Using confocal microscopy, we demonstrated that CXCR4 is colocalized with EEA‐1, Rab5, Rab4, and Rab11, which are localized in early and recycling endosomes. No significant colocalization of CXCR4 with lysosomal markers CD63 and Lamp‐1 was detected. Using antibody feeding experiments, we report a role for CXCR4 constitutive endocytosis in subcellular localization in stably transduced UT7‐CXCR4‐GFP and CD34+ cells. Agonist‐independent endocytosis of CXCR4 occurs through clathrin‐coated vesicles. These data implicate a constitutive endocytosis in the regulation of CXCR4 membrane expression and suggest that constitutive endocytosis may be involved in the regulation of trafficking the human hematopoietic progenitor/stem cells to and in the bone marrow microenvironment.</abstract><cop>Bristol</cop><pub>John Wiley & Sons, Ltd</pub><pmid>15536192</pmid><doi>10.1634/stemcells.22-6-1015</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antigens, CD - biosynthesis Antigens, CD34 - biosynthesis CD34+ cells Cell Membrane - metabolism Cell migration Cell Movement Chemotaxis Clathrin - metabolism CXCR4 receptor Endocytosis Flow Cytometry Gene Expression Regulation Green Fluorescent Proteins - metabolism Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Humans Ligands Lysosomal Membrane Proteins Membrane Proteins - biosynthesis Microscopy, Confocal Plasmids - metabolism Platelet Membrane Glycoproteins - biosynthesis rab GTP-Binding Proteins - biosynthesis rab4 GTP-Binding Proteins - biosynthesis rab5 GTP-Binding Proteins - biosynthesis Receptors, CXCR4 - biosynthesis Retroviridae - genetics SDF‐1 Signal Transduction Temperature Tetraspanin 30 Vesicular Transport Proteins |
title | Intracellular Localization and Constitutive Endocytosis of CXCR4 in Human CD34+ Hematopoietic Progenitor Cells |
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