Rac and Cdc42 GTPases Control Hematopoietic Stem Cell Shape, Adhesion, Migration, and Mobilization
Critical to homeostasis of blood cell production by hematopoietic stem/progenitor (HSC/P) cells is the regulation of HSC/P retention within the bone marrow microenvironment and migration between the bone marrow and the blood. Key extracellular regulatory elements for this process have been defined (...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2001-05, Vol.98 (10), p.5614-5618 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | F.-C. Yang Atkinson, S. J. Gu, Y. Borneo, J. B. Roberts, A. W. Zheng, Y. Pennington, J. Williams, D. A. |
| description | Critical to homeostasis of blood cell production by hematopoietic stem/progenitor (HSC/P) cells is the regulation of HSC/P retention within the bone marrow microenvironment and migration between the bone marrow and the blood. Key extracellular regulatory elements for this process have been defined (cell-cell adhesion, growth factors, chemokines), but the mechanism by which HSC/P cells reconcile multiple external signals has not been elucidated. Rac and related small GTPases are candidates for this role and were studied in HSC/P deficient in Rac2, a hematopoietic cell-specific family member. Rac2 appears to be critical for HSC/P adhesion both in vitro and in vivo, whereas a compensatory increase in Cdc42 activation regulates HSC/P migration. This genetic analysis provides physiological evidence of cross-talk between GTPase proteins and suggests that a balance of these two GTPases controls HSC/P adhesion and mobilization in vivo. |
| doi_str_mv | 10.1073/pnas.101546898 |
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Yang ; Atkinson, S. J. ; Gu, Y. ; Borneo, J. B. ; Roberts, A. W. ; Zheng, Y. ; Pennington, J. ; Williams, D. A.</creator><creatorcontrib>F.-C. Yang ; Atkinson, S. J. ; Gu, Y. ; Borneo, J. B. ; Roberts, A. W. ; Zheng, Y. ; Pennington, J. ; Williams, D. A.</creatorcontrib><description>Critical to homeostasis of blood cell production by hematopoietic stem/progenitor (HSC/P) cells is the regulation of HSC/P retention within the bone marrow microenvironment and migration between the bone marrow and the blood. Key extracellular regulatory elements for this process have been defined (cell-cell adhesion, growth factors, chemokines), but the mechanism by which HSC/P cells reconcile multiple external signals has not been elucidated. Rac and related small GTPases are candidates for this role and were studied in HSC/P deficient in Rac2, a hematopoietic cell-specific family member. Rac2 appears to be critical for HSC/P adhesion both in vitro and in vivo, whereas a compensatory increase in Cdc42 activation regulates HSC/P migration. This genetic analysis provides physiological evidence of cross-talk between GTPase proteins and suggests that a balance of these two GTPases controls HSC/P adhesion and mobilization in vivo.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.101546898</identifier><identifier>PMID: 11320224</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Antibodies ; Base Sequence ; Biological Sciences ; Blood ; Blood cells ; Bone marrow ; Bone marrow cells ; cdc42 GTP-Binding Protein - physiology ; Cell adhesion ; Cell Adhesion - physiology ; Cell lines ; Cell Movement - physiology ; Cell Size - physiology ; Cells ; Cellular biology ; DNA Primers ; Hematopoietic Stem Cells - cytology ; Mast cells ; Mice ; Mice, Inbred Strains ; rac GTP-Binding Proteins - physiology ; Stem cells</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2001-05, Vol.98 (10), p.5614-5618</ispartof><rights>Copyright 1993-2001 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences May 8, 2001</rights><rights>Copyright © 2001, The National Academy of Sciences 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-4999dd49395fe9b83e8e092080f3662af73ed332d44171c913dcfe9aa769423f3</citedby><cites>FETCH-LOGICAL-c553t-4999dd49395fe9b83e8e092080f3662af73ed332d44171c913dcfe9aa769423f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/98/10.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3055675$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3055675$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11320224$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>F.-C. Yang</creatorcontrib><creatorcontrib>Atkinson, S. J.</creatorcontrib><creatorcontrib>Gu, Y.</creatorcontrib><creatorcontrib>Borneo, J. B.</creatorcontrib><creatorcontrib>Roberts, A. W.</creatorcontrib><creatorcontrib>Zheng, Y.</creatorcontrib><creatorcontrib>Pennington, J.</creatorcontrib><creatorcontrib>Williams, D. A.</creatorcontrib><title>Rac and Cdc42 GTPases Control Hematopoietic Stem Cell Shape, Adhesion, Migration, and Mobilization</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Critical to homeostasis of blood cell production by hematopoietic stem/progenitor (HSC/P) cells is the regulation of HSC/P retention within the bone marrow microenvironment and migration between the bone marrow and the blood. Key extracellular regulatory elements for this process have been defined (cell-cell adhesion, growth factors, chemokines), but the mechanism by which HSC/P cells reconcile multiple external signals has not been elucidated. Rac and related small GTPases are candidates for this role and were studied in HSC/P deficient in Rac2, a hematopoietic cell-specific family member. Rac2 appears to be critical for HSC/P adhesion both in vitro and in vivo, whereas a compensatory increase in Cdc42 activation regulates HSC/P migration. This genetic analysis provides physiological evidence of cross-talk between GTPase proteins and suggests that a balance of these two GTPases controls HSC/P adhesion and mobilization in vivo.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Base Sequence</subject><subject>Biological Sciences</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Bone marrow</subject><subject>Bone marrow cells</subject><subject>cdc42 GTP-Binding Protein - physiology</subject><subject>Cell adhesion</subject><subject>Cell Adhesion - physiology</subject><subject>Cell lines</subject><subject>Cell Movement - physiology</subject><subject>Cell Size - physiology</subject><subject>Cells</subject><subject>Cellular biology</subject><subject>DNA Primers</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Mast cells</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>rac GTP-Binding Proteins - physiology</subject><subject>Stem cells</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc1v1DAQxS0EotuWKyeELA7tpSnjjzi2xKWKaIvUCkTL2fImTterJE5jBwF_PU53uxTEySPP7z290UPoNYFTAgV7P_QmpInkXEgln6EFAUUywRU8RwsAWmSSU76H9kNYA4DKJbxEe4QwCpTyBVp-NRU2fY3LuuIUX9x-McEGXPo-jr7Fl7Yz0Q_e2egqfBNth0vbtvhmZQZ7gs_qlQ3O9yf42t2NJj6Ms9u1X7rW_Xr4OUQvGtMG-2r7HqBv5x9vy8vs6vPFp_LsKqvynMWMK6Xqmium8saqpWRWWlAUJDRMCGqagtmaMVpzTgpSKcLqKoHGFEJxyhp2gD5sfIdp2dm6sukE0-phdJ0Zf2pvnP5707uVvvPfdTIVJMmPtvLR3082RN25UKVjTW_9FHQBkjFRQALf_QOu_TT26TRNgbAUjIoEnW6gavQhjLbZ5SCg5-b03JzeNZcEb5-m_4Nvq0rA8RaYhY9rJWfDXBCum6lto_0Rn1j9n0zAmw2wDtGPO4JBnosiZ78BG_K0xQ</recordid><startdate>20010508</startdate><enddate>20010508</enddate><creator>F.-C. 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| subjects | Animals Antibodies Base Sequence Biological Sciences Blood Blood cells Bone marrow Bone marrow cells cdc42 GTP-Binding Protein - physiology Cell adhesion Cell Adhesion - physiology Cell lines Cell Movement - physiology Cell Size - physiology Cells Cellular biology DNA Primers Hematopoietic Stem Cells - cytology Mast cells Mice Mice, Inbred Strains rac GTP-Binding Proteins - physiology Stem cells |
| title | Rac and Cdc42 GTPases Control Hematopoietic Stem Cell Shape, Adhesion, Migration, and Mobilization |
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