Faculty Opinions recommendation of Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration.

Cell migration is essential for various physiological and pathological processes. Polarization in motile cells requires the coordination of several key signaling molecules, including RhoA small GTPases and phosphoinositides. Although RhoA participates in a front–rear polarization in migrating cells, little is known about the functional interaction between RhoA and lipid turnover. We find here that src-homology 2–containing inositol-5-phosphatase 2 (SHIP2) interacts with RhoA in a GTP-dependent manner. The association between SHIP2 and RhoA is observed in spreading and migrating U251 glioma cells. The depletion of SHIP2 attenuates cell polarization and migration, which is rescued by wild-type SHIP2 but not by a mutant defective in RhoA binding. In addition, the depletion of SHIP2 impairs the proper localization of phosphatidylinositol 3,4,5-trisphosphate, which is not restored by a mutant defective in RhoA binding. These results suggest that RhoA associates with SHIP2 to regulate cell polarization and migration.

Download Full-text

CaM kinase IIδ2-dependent regulation of vascular smooth muscle cell polarization and migration

AJP Cell Physiology ◽

10.1152/ajpcell.90638.2007 ◽

2008 ◽

Vol 294 (6) ◽

pp. C1465-C1475 ◽

Cited By ~ 44

Author(s):

Melissa Z. Mercure ◽

Roman Ginnan ◽

Harold A. Singer

Keyword(s):

Smooth Muscle ◽

Cell Migration ◽

Vascular Smooth Muscle ◽

Cell Monolayer ◽

Leading Edge ◽

Cell Polarization ◽

Loss Of Function ◽

Downstream Signaling ◽

Transient Activation ◽

And Migration

Previous studies indicate involvement of the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) in vascular smooth muscle (VSM) cell migration. In the present study, molecular loss-of-function studies were used specifically to assess the role of the predominant CaMKIIδ2 isoform on VSM cell migration using a scratch wound healing assay. Targeted CaMKIIδ2 knockdown using siRNA or inhibition of activity by overexpressing a kinase-negative mutant resulted in attenuation of VSM cell migration. Temporal and spatial assessments of kinase autophosphorylation indicated rapid and transient activation in response to wounding, in addition to a sustained activation in the leading edge of migrating and spreading cells. Furthermore, siRNA-mediated suppression of CaMKIIδ2 resulted in the inhibition of wound-induced Rac activation and Golgi reorganization, and disruption of leading edge morphology, indicating an important function for CaMKIIδ2 in regulating VSM cell polarization. Numerous previous reports link activation of CaMKII to ERK1/2 signaling in VSM. Wound-induced ERK1/2 activation was also found to be dependent on CaMKII; however, ERK activity did not account for effects of CaMKII in regulating Golgi polarization, indicating alternative mechanisms by which CaMKII affects the complex events involved in cell migration. Wounding a VSM cell monolayer results in CaMKIIδ2 activation, which positively regulates VSM cell polarization and downstream signaling, including Rac and ERK1/2 activation, leading to cell migration.

Download Full-text

Microinjection of antibodies against talin inhibits the spreading and migration of fibroblasts

Journal of Cell Science ◽

10.1242/jcs.102.4.753 ◽

1992 ◽

Vol 102 (4) ◽

pp. 753-762

Author(s):

G.H. Nuckolls ◽

L.H. Romer ◽

K. Burridge

Keyword(s):

Extracellular Matrix ◽

Tissue Culture ◽

Actin Filaments ◽

Focal Adhesions ◽

Cell Spreading ◽

And Migration ◽

Extracellular Matrix Receptors

Talin is believed to be one of the key proteins involved in linking actin filaments to extracellular matrix receptors in focal adhesions. Our strategy for studying the function of talin has been to inactivate talin in living fibroblasts in tissue culture through the microinjection of affinity-purified, polyclonal anti-talin antibodies. The effect of the injected anti-talin antibodies on cell spreading was found to depend on how recently the cells had been plated. Cells that were in the process of spreading on a fibronectin substratum, and which had newly developed focal adhesions, were induced to round up and to disassemble many of the adhesions. However, if fibroblasts were allowed to spread completely before they were microinjected with the anti-talin antibody, focal adhesions remained intact and the flat morphology of the cells was unaffected. The percentage of cells that were able to maintain a spread morphology despite the injection of anti-talin antibodies increased during the first few hours after plating on fibronectin substrata. Fibroblasts that were allowed to spread completely before microinjection with the anti-talin antibody retained both intact focal adhesions and a flat, well-spread morphology, but failed to migrate effectively. Our experiments do not directly address the role of talin in mature focal adhesions, but they indicate that talin is essential for the spreading and migration of fibroblasts on fibronectin as well as for the development and initial maintenance of focal adhesions on this substratum.

Download Full-text

Cep70 contributes to angiogenesis by modulating microtubule rearrangement and stimulating cell polarization and migration

Cell Cycle ◽

10.4161/cc.19954 ◽

2012 ◽

Vol 11 (8) ◽

pp. 1554-1563 ◽

Cited By ~ 27

Author(s):

Xingjuan Shi ◽

Min Liu ◽

Dengwen Li ◽

Jun Wang ◽

Ritu Aneja ◽

...

Keyword(s):

Cell Polarization ◽

And Migration

Download Full-text

Kinases regulating Golgi apparatus structure and function.

Biochemical Society Symposium ◽

10.1042/bss0720015 ◽

2005 ◽

Vol 72 ◽

pp. 15-30 ◽

Cited By ~ 12

Author(s):

Christian Preisinger ◽

Francis A. Barr

Keyword(s):

Protein Kinases ◽

Cell Polarization ◽

Cyclin B ◽

Structural Proteins ◽

Protein Kinase D ◽

Cyclin Dependent Kinase ◽

Interphase Cells ◽

Mitogen Activated Protein ◽

And Migration ◽

And Function

Protein kinases control Golgi function in both mitotic and interphase cells. In mitosis, phosphorylation of structural proteins by Cdk1 (cyclin-dependent kinase 1)-cyclin B, Polo-like and mitogen-activated protein kinases underlie changes in Golgi reorganization during cell division. While in interphase, signalling pathways that are associated with the Golgi control secretory function through a variety of mechanisms. Some of these, notably those involving protein kinase D and Ste20 family kinases, are also relevant for the establishment and maintenance of cell polarization and migration.

Download Full-text