scholarly journals Stat3 promotes directional cell migration by regulating Rac1 activity via its activator  PIX

2009 ◽  
Vol 122 (22) ◽  
pp. 4150-4159 ◽  
Author(s):  
T. S. Teng ◽  
B. Lin ◽  
E. Manser ◽  
D. C. H. Ng ◽  
X. Cao
Keyword(s):  
Cell Migration ◽  
Rac1 Activity ◽  
Directional Cell Migration

scholarly journals Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway

2017 ◽  
Vol 114 (44) ◽  
pp. E9280-E9289 ◽  
Author(s):  
Takamasa Mizoguchi ◽  
Shoko Ikeda ◽  
Saori Watanabe ◽  
Michiko Sugawara ◽  
Motoyuki Itoh
Keyword(s):  
Cell Migration ◽  
Lateral Line ◽  
Wound Closure ◽  
Cultured Cells ◽  
Small Gtpase ◽  
Precise Control ◽  
Animal Development ◽  
Posterior Lateral Line ◽  
Rac1 Activity ◽  
Directional Cell Migration

Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood. Here, we show that the ubiquitin ligase mind bomb 1 (Mib1) is involved in persistent directional cell migration. We found that knockdown of MIB1 led to an increase in random cell migration in HeLa cells in a wound-closure assay. Furthermore, we explored novel Mib1 substrates for cell migration and found that Mib1 ubiquitinates Ctnnd1. Mib1-mediated ubiquitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1ta52b mutant showed increased random migration and loss of directional F-actin–based protrusion formation. Knockdown of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1ta52b mutant. Taken together, our data suggest that Mib1 plays an important role in cell migration and that persistent directional cell migration is regulated, at least in part, by the Mib1–Ctnnd1–Rac1 pathway.

scholarly journals α-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation

2015 ◽  
Vol 112 (15) ◽  
pp. E1926-E1935 ◽  
Author(s):  
Shijun Wang ◽  
Chun-Hsien Chu ◽  
Tessandra Stewart ◽  
Carmen Ginghina ◽  
Yifei Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Migration ◽  
Neuronal Damage ◽  
Directional Migration ◽  
Chronic Neuroinflammation ◽  
Tyrosine Protein Kinase ◽  
Microglial Migration ◽  
Directional Cell Migration ◽  
Cytoskeleton Rearrangement

Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson’s disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-syn aggregates act as chemoattractants to direct microglia toward damaged neurons. In addition, we describe a mechanism underlying this directional migration of microglia. Specifically, chemotaxis occurs when α-syn binds to integrin CD11b, leading to H2O2 production by NADPH oxidase. H2O2 directly attracts microglia via a process in which extracellularly generated H2O2 diffuses into the cytoplasm and tyrosine protein kinase Lyn, phosphorylates the F-actin–associated protein cortactin after sensing changes in the microglial intracellular concentration of H2O2. Finally, phosphorylated cortactin mediates actin cytoskeleton rearrangement and facilitates directional cell migration. These findings have significant implications, given that α-syn–mediated microglial migration reaches beyond Parkinson’s disease.

scholarly journals An Intact Centrosome Is Required for the Maintenance of Polarization during Directional Cell Migration

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15462 ◽  
Author(s):  
Nicole M. Wakida ◽  
Elliot L. Botvinick ◽  
Justin Lin ◽  
Michael W. Berns
Keyword(s):  
Cell Migration ◽  
Directional Cell Migration
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