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 (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.
Yang
F C
FC
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.
Atkinson
S J
SJ
Gu
Y
Y
Borneo
J B
JB
Roberts
A W
AW
Zheng
Y
Y
Pennington
J
J
Williams
D A
DA
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size / Q000502:physiology*; D017931:DNA Primers; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051379:Mice; D008815:Mice, Inbred Strains; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*
D017931:DNA Primers; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins