Cep70 contributes to angiogenesis by modulating microtubule rearrangement and stimulating 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.

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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.

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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.

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Ligand slope, density and affinity direct cell polarity and migration on molecular gradient surfaces

RSC Advances ◽

10.1039/c4ra03795b ◽

2014 ◽

Vol 4 (60) ◽

pp. 31581-31588 ◽

Cited By ~ 11

Author(s):

Eun-ju Lee ◽

Eugene W. L. Chan ◽

Wei Luo ◽

Muhammad N. Yousaf

Keyword(s):

Cell Polarity ◽

Cell Polarization ◽

Gradient Surfaces ◽

Direct Cell ◽

And Migration

A patterned peptide gradient with control of slope and density is created for studies of directed cell polarization and migration.

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Synthetic Activation of Endogenous PI3K and Rac Identifies an AND-Gate Switch for Cell Polarization and Migration

PLoS ONE ◽

10.1371/journal.pone.0003068 ◽

2008 ◽

Vol 3 (8) ◽

pp. e3068 ◽

Cited By ~ 90

Author(s):

Takanari Inoue ◽

Tobias Meyer

Keyword(s):

Cell Polarization ◽

And Migration

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Coordination of cell polarization and migration by the Rho family GTPases requires Src tyrosine kinase activity

Current Biology ◽

10.1016/s0960-9822(01)00583-8 ◽

2001 ◽

Vol 11 (23) ◽

pp. 1836-1846 ◽

Cited By ~ 127

Author(s):

Paul Timpson ◽

Gareth E. Jones ◽

Margaret C. Frame ◽

Valerie G. Brunton

Keyword(s):

Tyrosine Kinase ◽

Kinase Activity ◽

Cell Polarization ◽

Tyrosine Kinase Activity ◽

Src Tyrosine Kinase ◽

Rho Family Gtpases ◽

Rho Family ◽

And Migration

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Actin Waves: Origin of Cell Polarization and Migration?

Trends in Cell Biology ◽

10.1016/j.tcb.2017.02.003 ◽

2017 ◽

Vol 27 (7) ◽

pp. 515-526 ◽

Cited By ~ 57

Author(s):

Naoyuki Inagaki ◽

Hiroko Katsuno

Keyword(s):

Cell Polarization ◽

Actin Waves ◽

And Migration

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Shear stress–induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases

The Journal of Cell Biology ◽

10.1083/jcb.200210135 ◽

2003 ◽

Vol 161 (2) ◽

pp. 429-439 ◽

Cited By ~ 219

Author(s):

Beata Wojciak-Stothard ◽

Anne J. Ridley

Keyword(s):

Shear Stress ◽

Cell Shape ◽

Rho Kinase ◽

Cell Movement ◽

Cell Polarization ◽

Migration Speed ◽

Rhoa Activity ◽

Endothelial Response ◽

And Migration ◽

Shape Changes

Shear stress induces endothelial polarization and migration in the direction of flow accompanied by extensive remodeling of the actin cytoskeleton. The GTPases RhoA, Rac1, and Cdc42 are known to regulate cell shape changes through effects on the cytoskeleton and cell adhesion. We show here that all three GTPases become rapidly activated by shear stress, and that each is important for different aspects of the endothelial response. RhoA was activated within 5 min after stimulation with shear stress and led to cell rounding via Rho-kinase. Subsequently, the cells respread and elongated within the direction of shear stress as RhoA activity returned to baseline and Rac1 and Cdc42 reached peak activation. Cell elongation required Rac1 and Cdc42 but not phosphatidylinositide 3-kinases. Cdc42 and PI3Ks were not required to establish shear stress–induced polarity although they contributed to optimal migration speed. Instead, Rho and Rac1 regulated directionality of cell movement. Inhibition of Rho or Rho-kinase did not affect the cell speed but significantly increased cell displacement. Our results show that endothelial cells reorient in response to shear stress by a two-step process involving Rho-induced depolarization, followed by Rho/Rac-mediated polarization and migration in the direction of flow.

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