scholarly journals Regulation of Immature Dendritic Cell Migration by RhoA Guanine Nucleotide Exchange Factor Arhgef5

2009 ◽  
Vol 284 (42) ◽  
pp. 28599-28606 ◽  
Author(s):  
Zhenglong Wang ◽  
Yosuke Kumamoto ◽  
Ping Wang ◽  
Xiaoqing Gan ◽  
David Lehmann ◽  
...  
Keyword(s):  
Cell Migration ◽  
Dendritic Cell ◽  
Guanine Nucleotide Exchange Factor ◽  
Immature Dendritic Cell ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Exchange Factor ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Dendritic Cell Migration

Trio amino-terminal guanine nucleotide exchange factor domain expression promotes actin cytoskeleton reorganization, cell migration and anchorage-independent cell growth

1999 ◽  
Vol 112 (12) ◽  
pp. 1825-1834 ◽  
Author(s):  
K. Seipel ◽  
Q.G. Medley ◽  
N.L. Kedersha ◽  
X.A. Zhang ◽  
S.P. O'Brien ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Growth ◽  
Actin Cytoskeleton ◽  
Guanine Nucleotide Exchange Factor ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Exchange Factor ◽  
Amino Terminal ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor

Rho family GTPases regulate diverse cellular processes, including extracellular signal-mediated actin cytoskeleton reorganization and cell growth. The functions of GTPases are positively regulated by guanine nucleotide exchange factors, which promote the exchange of GDP for GTP. Trio is a complex protein possessing two guanine nucleotide exchange factor domains, each with adjacent pleckstrin homology and SH3 domains, a protein serine/threonine kinase domain with an adjacent immunoglobulin-like domain and multiple spectrin-like domains. To assess the functional role of the two Trio guanine nucleotide exchange factor domains, NIH 3T3 cell lines stably expressing the individual guanine nucleotide exchange factor domains were established and characterized. Expression of the amino-terminal guanine nucleotide exchange factor domain results in prominent membrane ruffling, whereas cells expressing the carboxy-terminal guanine nucleotide exchange factor domain have lamellae that terminate in miniruffles. Moreover, cells expressing the amino-terminal guanine nucleotide exchange factor domain display more rapid cell spreading, haptotactic cell migration and anchorage-independent growth, suggesting that Trio regulates both cell motility and cell growth. Expression of full-length Trio in COS cells also alters actin cytoskeleton organization, as well as the distribution of focal contact sites. These findings support a role for Trio as a multifunctional protein that integrates and amplifies signals involved in coordinating actin remodeling, which is necessary for cell migration and growth.

scholarly journals Guanine Nucleotide Exchange Factor-H1 Regulates Cell Migration via Localized Activation of RhoA at the Leading Edge

2009 ◽  
Vol 20 (18) ◽  
pp. 4070-4082 ◽  
Author(s):  
Perihan Nalbant ◽  
Yuan-Chen Chang ◽  
Jörg Birkenfeld ◽  
Zee-Fen Chang ◽  
Gary M. Bokoch
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Leading Edge ◽  
Guanine Nucleotide Exchange Factor ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Exchange Factor ◽  
Rhoa Activity ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor

Cell migration involves the cooperative reorganization of the actin and microtubule cytoskeletons, as well as the turnover of cell–substrate adhesions, under the control of Rho family GTPases. RhoA is activated at the leading edge of motile cells by unknown mechanisms to control actin stress fiber assembly, contractility, and focal adhesion dynamics. The microtubule-associated guanine nucleotide exchange factor (GEF)-H1 activates RhoA when released from microtubules to initiate a RhoA/Rho kinase/myosin light chain signaling pathway that regulates cellular contractility. However, the contributions of activated GEF-H1 to coordination of cytoskeletal dynamics during cell migration are unknown. We show that small interfering RNA-induced GEF-H1 depletion leads to decreased HeLa cell directional migration due to the loss of the Rho exchange activity of GEF-H1. Analysis of RhoA activity by using a live cell biosensor revealed that GEF-H1 controls localized activation of RhoA at the leading edge. The loss of GEF-H1 is associated with altered leading edge actin dynamics, as well as increased focal adhesion lifetimes. Tyrosine phosphorylation of focal adhesion kinase and paxillin at residues critical for the regulation of focal adhesion dynamics was diminished in the absence of GEF-H1/RhoA signaling. This study establishes GEF-H1 as a critical organizer of key structural and signaling components of cell migration through the localized regulation of RhoA activity at the cell leading edge.

scholarly journals The Rho-guanine nucleotide exchange factor Solo decelerates collective cell migration by modulating the Rho-ROCK pathway and keratin networks

2020 ◽  
Vol 31 (8) ◽  
pp. 741-752 ◽  
Author(s):  
Yusuke Isozaki ◽  
Kouki Sakai ◽  
Kenta Kohiro ◽  
Katsuhiko Kagoshima ◽  
Yuma Iwamura ◽  
...  
Keyword(s):  
Cell Migration ◽  
Guanine Nucleotide Exchange Factor ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Exchange Factor ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Keratin 18

Collective cell migration is crucial for tissue remodeling and cancer invasion. A RhoA-targeting guanine nucleotide exchange factor, Solo, localizes to the cell–cell contact sites in collectively migrating cells and acts as a brake for collective cell migration via promoting the RhoA-ROCK pathway and regulating the keratin-8/keratin-18 networks.

scholarly journals DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses

Blood ◽  
2012 ◽  
Vol 119 (19) ◽  
pp. 4451-4461 ◽  
Author(s):  
Yosuke Harada ◽  
Yoshihiko Tanaka ◽  
Masao Terasawa ◽  
Markus Pieczyk ◽  
Katsuyoshi Habiro ◽  
...  
Keyword(s):  
Leading Edge ◽  
Guanine Nucleotide Exchange Factor ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Exchange Factor ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Subcapsular Sinus ◽  
Dendritic Cell Migration ◽  
And Migration

Abstract To migrate efficiently through the interstitium, dendritic cells (DCs) constantly adapt their shape to the given structure of the extracellular matrix and follow the path of least resistance. It is known that this amoeboid migration of DCs requires Cdc42, yet the upstream regulators critical for localization and activation of Cdc42 remain to be determined. Mutations of DOCK8, a member of the atypical guanine nucleotide exchange factor family, causes combined immunodeficiency in humans. In the present study, we show that DOCK8 is a Cdc42-specific guanine nucleotide exchange factor that is critical for interstitial DC migration. By generating the knockout mice, we found that in the absence of DOCK8, DCs failed to accumulate in the lymph node parenchyma for T-cell priming. Although DOCK8-deficient DCs migrated normally on 2-dimensional surfaces, DOCK8 was required for DCs to crawl within 3-dimensional fibrillar networks and to transmigrate through the subcapsular sinus floor. This function of DOCK8 depended on the DHR-2 domain mediating Cdc42 activation. DOCK8 deficiency did not affect global Cdc42 activity. However, Cdc42 activation at the leading edge membrane was impaired in DOCK8-deficient DCs, resulting in a severe defect in amoeboid polarization and migration. Therefore, DOCK8 regulates interstitial DC migration by controlling Cdc42 activity spatially.

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