Rapid TGFβ1 effects on actin cytoskeleton of astrocytes: Comparison with other factors and implications for cell motility

Gagelin, Claire; Martineau, Pierre; Gavaret, Jean‐Michel; Toru-Delbauffe, D.

doi:10.1002/glia.440130405

Cited by 43 publications

(32 citation statements)

References 61 publications

(72 reference statements)

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“…Since actin cytoskeleton is continuously remodeled in astrocytes by second-messenger changes (Goldman and Chiu, 1984;Farwell et al, 1990;Gagelin et al, 1995;Blobe et al, 1996) and is also affected by PKC phosphorylation itself (Blobe et al, 1996), it is conceivable that remodeling of actin cytoskeleton could be involved in the plasticity of PKC-␤II targeting.…”

Section: Discussionmentioning

confidence: 98%

Translocation of protein kinase C‐βII in astrocytes requires organized actin cytoskeleton and is not accompanied by synchronous RACK1 relocation

Pascale¹,

Alkon²,

Grimaldi³

2004

Glia

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Protein kinase C (PKC)-betaII is the most abundant PKC isoform in astrocytes. Upon activation, this isoform of PKC translocates from the cytosol to the plasma membrane (PM). In this study, we investigated in astrocytes the modality of PKC-betaII translocation as far as the participation of the receptor for activated C kinase-1 (RACK1) and the requirement for intact cytoskeleton in the process. In astrocytes, Western blots and immunocytochemistry coupled to confocal microscopic quantitative analysis showed that after 5 min of phorbol-12-myristate-13-acetate (PMA) exposure, native PKC-betaII, but not PKC-betaI, is relocated efficiently from the cytosol to the PM. Translocation of PKC-betaII was not associated with synchronous RACK1 relocation. Furthermore, the quantity of PM-associated PKC-betaII that co-immunoprecipitated with PM-bound RACK1 increased following PMA exposure, indicating a post activation binding of the two proteins in the PM. Because RACK1 and PKC-betaII relocation seemed not to be synchronous, we hypothesized that an intermediate interaction with the cytoskeleton was taking place. In fact, we were able to show that pharmacological disruption of actin-based cytoskeleton greatly deranged PKC-betaII translocation to the PM. The requirement for intact actin cytoskeleton was specific, because depolymerization of tubulin had no effect on the ability of the kinase to translocate to the PM. These results indicate that in astrocytes, RACK1 and PKC-betaII synchronous relocation is not essential for relocation of PKC-betaII to the PM. In addition, we show for the first time that the integrity of the actin cytoskeleton plays a specific role in PKC-betaII movements in these cells. We hypothesize that in glial cells, rapidly occurring changes of actin cytoskeleton arrangement may be involved in the fast reprogramming of PKC targeting to specific PM location to phosphorylate substrates in different cellular locations.

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Section: Discussionmentioning

confidence: 98%

Translocation of protein kinase C‐βII in astrocytes requires organized actin cytoskeleton and is not accompanied by synchronous RACK1 relocation

Pascale¹,

Alkon²,

Grimaldi³

2004

Glia

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“…TGF-␤s have been shown to elicit profound effects on the actin cytoskeleton and stress fibers, enhance the expression of GFAP, and inhibit the proliferation in cultured cerebellar astrocytes (63)(64)(65). The Smad4…”

Section: Discussionmentioning

confidence: 99%

Cerebellar Deficits and Hyperactivity in Mice Lacking Smad4

Zhou

Zhao

et al. 2003

Journal of Biological Chemistry

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Smad4 is a central mediator of TGF-␤ signals, which are known to play essential roles in many biological processes. Using a Cre-loxP approach to overcome early embryonic lethality, we have studied functions of TGF-␤/Smad4 signals in the central nervous system (CNS). No obvious deficits were detected in mice carrying the targeted disruption of Smad4 in the CNS. The overall morphology of the hippocampus appeared normal. There was no change in the proliferation of neuronal precursor cells, nor in several forms of synaptic plasticity. In contrast, deletion of Smad4 resulted in a marked decrease in the number of cerebellar Purkinje cells and parvalbumin-positive interneurons. Accompanied by the abnormality in the cerebellum, mutant mice also exhibited significantly increased vertical activity. Thus, our study reveals an unexpected role for Smad4 in cerebellar development and in the control of motor function.

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“…Similar effects have also been seen in various cell lines following growth factor stimulation (33,34). In addition, cAMP inhibits growth factor-stimulated expression of G 1 phase, cyclins D1 and E, and the activation of cyclin A-and cyclin E-dependent histone H1 kinases (33,35,36). Cyclic AMP induces G 1 arrest, increases the critical cell size required for budding, and inhibits the expression of G 1 phase cyclins, CLN1 and CLN2, in yeast.…”

Section: Fig 6 Inhibition Of Egf-stimulated Cdk 2 Expression By Campmentioning

confidence: 99%

Coupling of Epidermal Growth Factor (EGF) with the Antiproliferative Activity of cAMP Induces Neuronal Differentiation

Mark

Storm

1997

Journal of Biological Chemistry

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Nerve growth factor (NGF) functions as a progression factor with both mitogenic and antimitogenic activities. When PC12 cells are treated with NGF, they advance to the G 1 stage of the cell cycle before they differentiate. The correlation between cessation of proliferation and differentiation suggests that the antimitotic activity of NGF may be obligatory for differentiation. Although epidermal growth factor-(EGF) and NGF-treated PC12 cells share several common properties, including activation of the mitogen-activated protein (MAP) kinase pathway and induction of immediate early genes, EGF is mitogenic for PC12 cells and does not normally stimulate differentiation. However, combinations of EGF and low levels of cAMP stimulate differentiation even though neither agent alone does (Mark, M. D., Liu, Y., Wong, S. T., Hinds, T. R., and Storm, D.R. (1995) J. Cell Biol. 130, 701-710). Since EGF is mitogenic for PC12 cells and differentiation may not occur until proliferation is inhibited, differentiation caused by cAMP and EGF may be due to the antiproliferative activity of cAMP. To test this hypothesis, we examined the effect of EGF or combinations of EGF and cAMP on PC12 cell proliferation. EGF alone stimulated proliferation of PC12 cells and increased the levels of several cell cycle progression factors including cdk2, cdk4, and cyclin B1. Cyclic AMP inhibited the EGF-stimulated increases in cell cycle progression factors as well as proliferation. Other antiproliferative agents including rapamycin, mimosine, and nitric oxide agonists also synergized with EGF to stimulate differentiation. These data indicate that the coupling of antiproliferative signals with EGF modifies the biological properties of EGF and converts it to a differentiating growth factor. Neuronal differentiation of PC12 cells by nerve growth factor (NGF)1 is characterized by several changes including growth arrest, activation of specific genes, and neuritogenesis. A critical step for differentiation is arrest of the cell cycle. Although NGF treatment initially stimulates proliferation, this is followed by cessation of DNA synthesis and cell division (1-4). In addition, an asynchronous population of PC12 cells accumulates in a G 1 -like state following NGF treatment (5, 6). These findings imply that the cessation of cell proliferation in G 1 may be crucial for neuronal differentiation. Although the mechanism by which NGF arrests PC12 cells in G 1 phase is not fully understood, there appears to be a direct correlation between the differential regulation of specific cell cycle regulatory components and NGF-induced differentiation (1, 7).EGF-and NGF-treated PC12 cells share several common properties, including activation of the MAP kinase pathway, induction of immediate early genes (IEGs), membrane ruffling, and increased cell adhesion (8 -12). In contrast to NGF, EGF is a potent mitogen that does not stimulate differentiation (13). However, the molecular mechanisms differentiating these two growth factors are not fully understood. EGF, in combination w...

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Rapid TGFβ1 effects on actin cytoskeleton of astrocytes: Comparison with other factors and implications for cell motility

Cited by 43 publications

References 61 publications

Translocation of protein kinase C‐βII in astrocytes requires organized actin cytoskeleton and is not accompanied by synchronous RACK1 relocation

Translocation of protein kinase C‐βII in astrocytes requires organized actin cytoskeleton and is not accompanied by synchronous RACK1 relocation

Cerebellar Deficits and Hyperactivity in Mice Lacking Smad4

Coupling of Epidermal Growth Factor (EGF) with the Antiproliferative Activity of cAMP Induces Neuronal Differentiation

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