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Proc Natl Acad Sci U S A. 2001 May 8;98(10):5614-8. Epub 2001 Apr 24.

Rac and Cdc42 GTPases control hematopoietic stem cell shape, adhesion, migration, and mobilization.

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1
Howard Hughes Medical Institute, Section of Pediatric Hematology/Oncology, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Abstract

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.

PMID:
11320224
PMCID:
PMC33261
DOI:
10.1073/pnas.101546898
[Indexed for MEDLINE]
Free PMC Article
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