Cell shape regulation by Gravin requires N-terminal membrane effector domains

Weiser, Douglas C.; Julien, Krystal R. St.; Lang, James S.; Kimelman, David

doi:10.1016/j.bbrc.2008.08.063

Cited by 6 publications

(5 citation statements)

References 19 publications

(34 reference statements)

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“…Overexpression of SSeCKS was reported to inhibit cellular migration and alter cytoskeletal organization and cell shape in several cultured cell types and to inhibit the growth of prostate tumor cells in nude mice [20–25]. Along similar lines, Weiser et al [26] recently reported that gravin regulates cell spreading in COS7 cells. A report by Lee et al [27] further suggests that SSeCKS expression in astrocytes may regulate endothelial permeability at the blood brain barrier.…”

Section: Introductionmentioning

confidence: 99%

Gravin dynamics regulates the subcellular distribution of PKA

Yan

Walkiewicz

Carlson

et al. 2009

Experimental Cell Research

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Gravin, a multivalent A-kinase anchoring protein (AKAP), localizes to the cell periphery in several cell types and is postulated to target PKA and other binding partners to the plasma membrane. An N-terminal myristoylation sequence and three regions rich in basic amino acids are proposed to mediate this localization. Reports indicating that phorbol ester affects the distribution of SSeCKS, the rat orthologue of gravin, further suggest that PKC may also regulate the subcellular distribution of gravin, which in turn may affect PKA distribution. In this study, quantitative confocal microscopy of cells expressing full-length and mutant gravin-EGFP constructs lacking the proposed targeting domains revealed that either the N-myristoylation site or the polybasic regions were sufficient to target gravin to the cell periphery. Moreover, phorbol ester treatment induced redistribution of gravin-EGFP from the cell periphery to a juxtanuclear vesicular compartment, but this required the presence of the N-myristoylation site. Confocal microscopy further revealed that not only did gravin-EGFP target a PKA RII-ECFP construct to the cell periphery, but PKC activation resulted in redistribution of the gravin and PKA constructs to the same subcellular site. It is postulated that this dynamic response by gravin to PKC activity may mediate PKC dependent control of PKA activity.

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Section: Introductionmentioning

confidence: 99%

Gravin dynamics regulates the subcellular distribution of PKA

Yan

Walkiewicz

Carlson

et al. 2009

Experimental Cell Research

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“…Indeed, mouse AKAP12 was identified independently as a phosphatidylserine-binding protein (16, 24), a function that maps to the effector domains and that facilitates association with plasma membranes and PKC (13). The three effector domains are required for AKAP12 to mediate cell flattening (25). …”

Section: Introductionmentioning

confidence: 99%

Emerging Roles for SSeCKS/Gravin/AKAP12 in the Control of Cell Proliferation, Cancer Malignancy, and Barriergenesis

Gelman

2010

Genes & Cancer

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Emerging data suggest that SSeCKS/Gravin/AKAP12 (“AKAP12”), originally identified as an autoantigen in cases of myasthenia gravis, controls multiple biological processes through its ability to scaffold key signaling proteins such as protein kinase (PK) C and A, calmodulin, cyclins, phosphoinositides, the so-called “long” β-1,4 galactosyltransferase (GalTase) isoform, Src, as well as the actin cytoskeleton in a spatiotemporal manner. Specialized functions attributed to AKAP12 include the suppression of cancer malignancy- especially aspects of metastatic progression, regulation of blood-brain and blood-retina barrier formation, and re-sensitization of β2-adrenergic pain receptors. Recent data identify a direct role for AKAP12 in cytokinesis completion, further suggesting a function as a negative regulator of cell senescence. The current review will discuss the emerging knowledge base of AKAP12-related biological roles, and how the factors that affect AKAP12 expression or that interact with AKAP12 at the protein level control cancer progression and blood-tissue barrier formation.

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“…The non-canonical Wnts activate several downstream PCP effectors, including the small GTPase Rho, which mediates many of the effects of the PCP pathway during gastrulation (Habas et al, 2003;Marlow et al, 2002) by affecting cell polarity, cell shape changes and movement (Etienne-Manneville and Hall, 2002;Hall, 1998). Although most work on small G-proteins during gastrulation has focused on the role of non-canonical Wnts in controlling their activity (Habas et al, 2003), several other regulators of Rho are required for proper gastrulation, including the scaffolding protein Gravin (Akap12), which is essential for mesodermal cells to convert from amoeboid cell movement to intercalative cell behaviors at the end of gastrulation in order for extension to occur (Weiser et al, 2007;Weiser et al, 2008). RhoA activates the Formins, which control actin polymerization, and Rho-dependent kinase (Rock), which phosphorylates the regulatory light chain of non-muscle myosin (Mlc) (Etienne-Manneville and Hall, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Cells were transfected as described (Weiser et al, 2008). Conditioned media were obtained by culturing L-cells or Wnt5a/L-cells in DMEM containing 10% FBS without selective antibiotics for 5 days.…”

Section: Mammalian Tissue Culturementioning

confidence: 99%

Rho-regulated Myosin phosphatase establishes the level of protrusive activity required for cell movements during zebrafish gastrulation

2009

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Rho-dependent amoeboid cell movement is a crucial mechanism in both tumor cell invasion and morphogenetic cell movements during fish gastrulation. Amoeboid movement is characterized by relatively non-polarized cells displaying a high level of bleb-like protrusions. During gastrulation, zebrafish mesodermal cells undergo a series of conversions from amoeboid cell behaviors to more mesenchymal and finally highly polarized and intercalative cell behaviors. We demonstrate that Myosin phosphatase, a complex of Protein phosphatase 1 and the scaffolding protein Mypt1, functions to maintain the precise balance between amoeboid and mesenchymal cell behaviors required for cells to undergo convergence and extension. Importantly, Mypt1 has different cellautonomous and non-cell-autonomous roles. Loss of Mypt1 throughout the embryo causes severe convergence defects, demonstrating that Mypt1 is required for the cell-cell interactions involved in dorsal convergence. By contrast, mesodermal Mypt1 morphant cells transplanted into wild-type hosts undergo dorsally directed cell migration, but they fail to shut down their protrusive behavior and undergo the normal intercalation required for extension. We further show that Mypt1 activity is regulated in embryos by Rho-mediated inhibitory phosphorylation, which is promoted by non-canonical Wnt signaling. We propose that Myosin phosphatase is a crucial and tightly controlled regulator of cell behaviors during gastrulation and that understanding its role in early development also provides insight into the mechanism of cancer cell invasion.

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Cell shape regulation by Gravin requires N-terminal membrane effector domains

Cited by 6 publications

References 19 publications

Gravin dynamics regulates the subcellular distribution of PKA

Gravin dynamics regulates the subcellular distribution of PKA

Emerging Roles for SSeCKS/Gravin/AKAP12 in the Control of Cell Proliferation, Cancer Malignancy, and Barriergenesis

Rho-regulated Myosin phosphatase establishes the level of protrusive activity required for cell movements during zebrafish gastrulation

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