|
|
Blood, 15 October 2006, Vol. 108, No. 8, pp. 2814-2820.
Prepublished online as a Blood First Edition Paper on June 29, 2006; DOI 10.1182/blood-2006-01-010363.
 Previous Article | Next Article 
Submitted January 26, 2006
Accepted June 7, 2006
Rac1 links leading edge and uropod events through Rho
and myosin activation during chemotaxis
Kersi N Pestonjamasp, Carol Forster, Chunxiang Sun, Elisabeth M Gardiner, Ben Bohl, Orion Weiner, Gary M Bokoch, and Michael Glogauer*
Departments of Immunology and Cell Biology-IMM14, The Scripps Research Institute, La Jolla, CA, USA
University of Toronto, Toronto, Ontario, Canada
University of California San Francisco, CA, USA
* Corresponding author; email: michael.glogauer{at}utoronto.ca.
Chemotactic responsiveness is crucial to
neutrophil recruitment to sites of infection. During
chemotaxis, highly divergent cytoskeletal programs are
executed at the leading and trailing edge of motile
neutrophils. The Rho family small GTPases play critical
roles in cell migration, and recent work has focused on
elucidating the specific roles played by Rac1, Rac2,
Cdc42 and Rho during cellular chemotaxis. Rac GTPases
regulate actin polymerization and extension of the
leading edge, whereas Rho GTPases control myosin-based
contraction of the trailing edge. Rac and Rho signalling
are thought to crosstalk with one another, and previous
research has focused on mutual inhibition of Rac and Rho
signalling during chemotaxis. Indeed, polarization of
neutrophils has been proposed to involve the activity of
a negative feedback system where Rac activation at the
front of the cell inhibits local Rho activation, and
vice versa. Using primary human neutrophils and
neutrophils derived from a Rac1/Rac2 null transgenic
mouse model, we demonstrate here that Rac1 (and not
Rac2) is essential for Rho and myosin activation at the
trailing edge to regulate uropod function. We conclude
that Rac plays both positive and negative roles in the
organization of the Rho-myosin "backness" program,
thereby promoting stable polarity in chemotaxing
neutrophils.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
Neutrophil chemotaxis: a tail of 2 GTPases
- Mary C. Dinauer
Blood 2006 108: 2502.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
F. Wang
The Signaling Mechanisms Underlying Cell Polarity and Chemotaxis
Cold Spring Harb Perspect Biol,
October 1, 2009;
1(4):
a002980 - a002980.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zhang, C. Sun, M. Glogauer, and G. M. Bokoch
Human Neutrophils Coordinate Chemotaxis by Differential Activation of Rac1 and Rac2
J. Immunol.,
August 15, 2009;
183(4):
2718 - 2728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Phillipson, B. Heit, S. A. Parsons, B. Petri, S. C. Mullaly, P. Colarusso, R. M. Gower, G. Neely, S. I. Simon, and P. Kubes
Vav1 Is Essential for Mechanotactic Crawling and Migration of Neutrophils out of the Inflamed Microvasculature
J. Immunol.,
June 1, 2009;
182(11):
6870 - 6878.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Shi, J. Zhang, M. Mullin, B. Dong, A. S. Alberts, and K. A. Siminovitch
The mDial Formin Is Required for Neutrophil Polarization, Migration, and Activation of the LARG/RhoA/ROCK Signaling Axis during Chemotaxis
J. Immunol.,
March 15, 2009;
182(6):
3837 - 3845.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Mitchell, A. Lo, M. R. Logan, P. Lacy, and G. Eitzen
Primary granule exocytosis in human neutrophils is regulated by Rac-dependent actin remodeling
Am J Physiol Cell Physiol,
November 1, 2008;
295(5):
C1354 - C1365.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bagorda and C. A. Parent
Eukaryotic chemotaxis at a glance
J. Cell Sci.,
August 15, 2008;
121(16):
2621 - 2624.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Herrera Abreu, P. Castellanos Penton, V. Kwok, E. Vachon, D. Shalloway, L. Vidali, W. Lee, C. A. McCulloch, and G. P. Downey
Tyrosine phosphatase PTP{alpha} regulates focal adhesion remodeling through Rac1 activation
Am J Physiol Cell Physiol,
April 1, 2008;
294(4):
C931 - C944.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. V. Pajcini, J. H. Pomerantz, O. Alkan, R. Doyonnas, and H. M. Blau
Myoblasts and macrophages share molecular components that contribute to cell-cell fusion
J. Cell Biol.,
March 5, 2008;
180(5):
1005 - 1019.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. He, Z.-H. Qiao, J. Cai, W. Pierce, D.-C. He, and Z.-H. Song
Involvement of the 90-kDa Heat Shock Protein (Hsp-90) in CB2 Cannabinoid Receptor-Mediated Cell Migration: A New Role of Hsp-90 in Migration Signaling of a G Protein-Coupled Receptor
Mol. Pharmacol.,
November 1, 2007;
72(5):
1289 - 1300.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. X. Sun, M. A.O. Magalhaes, and M. Glogauer
Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptor
J. Cell Biol.,
October 22, 2007;
179(2):
239 - 245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-D. Filippi, K. Szczur, C. E. Harris, and P.-Y. Berclaz
Rho GTPase Rac1 is critical for neutrophil migration into the lung
Blood,
February 1, 2007;
109(3):
1257 - 1264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
