Distinct cellular effects and interactions of the Rho-family GTPase TC10

Neudauer, Cheryl L.; Joberty, Gérard; Tatsis, Nia; Macara, Ian G.

doi:10.1016/s0960-9822(07)00486-1

Cited by 127 publications

(142 citation statements)

References 41 publications

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“…In support of the classi®cation of TC10 as a Rho family GTPase, it has been reported recently that activated TC10 interacts with a variety of putative Rho family e ectors, stimulates JNK, and induces ®lopodial formation (Neudauer et al, 1998). In this communication, we con®rm many of these ®ndings and expand the study of this Rho family GTPase to include other signaling pathways as well as cellular transformation.…”

Section: Introductionsupporting

confidence: 63%

“…Similar to the action of CDC42 on the actin cytoskeleton, activated TC10 induces the formation of ®lopodia, and like CDC42 and Rac, activated TC10 stimulates JNK. Both of these properties were also observed by Neudauer et al (1998). In common with CDC42, Rac, and Rho, activated TC10 stimulates SRF-and NF-kB-dependent transcription and cooperates with Raf-CAAX in a synergistic focus forming transformation assay.…”

Section: Discussionmentioning

confidence: 76%

“…Moreover, a recent report (Neudauer et al, 1998) indicates that the ®lopodia induced by TC10 75L are signi®cantly longer than those induced by CDC42 61L, and that cells expressing TC10 75L produce nearly twice as many extensions as cells expressing CDC42 61L. In addition, detailed time-lapse images of cells expressing TC10 75L indicate that the actin structures formed are indeed ®lopodial extensions rather than retraction ®bers (Neudauer et al, 1998).…”

Section: Discussionmentioning

confidence: 97%

“…The level of TC10 expression was similar for all samples To con®rm the TC10-pro®lin interaction in vitro, we used a solution binding assay based on the interaction of immobilized His-tagged TC10 with a GST-pro®lin fusion protein. We also included a binding study to a GST-PAK3 protein fragment (CRIB domain) to con®rm this reported TC10 interaction (Neudauer et al, 1998). As shown in Figure 11a, TC10.GTP, but not TC10.GDP, interacts with PAK, and as shown in Figure 11b, TC10.GTP, and to a lesser extent TC10.GDP, interacts with pro®lin I (generated from a monocyte cDNA library by PCR).…”

Section: Tc10 Binds Pro®lin a Mediator Of Actin ®Lament Formationmentioning

confidence: 88%

“…e 7=less than 10% of 75L induction in COS cells cotransfected with TC10 and a luciferase expressing construct containing an upstream NF-kB binding site; +=less than 15% 75L induction. f focus forming assay in NIH3T3 cells observation (Neudauer et al, 1998) that this mutant, but not wild type TC10, is resistant to a Rho family GAP (p50RhoGAP), suggest that this is a typical GTPase defective mutant that will be bound predominantly to GTP in vivo. It should also be noted that, in contrast to p50RhoGAP, no TC10 e ective GEF has yet been reported (Hart et al, 1994;Zheng et al, 1995;Ren et al, 1998).…”

Section: Discussionmentioning

confidence: 98%

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Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth

Murphy

Solski²,

Jillian

et al. 1999

Oncogene

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The small Ras-related GTPase, TC10, has been classi®ed on the basis of sequence homology to be a member of the Rho family. This family, which includes the Rho, Rac and CDC42 subfamilies, has been shown to regulate a variety of apparently diverse cellular processes such as actin cytoskeletal organization, mitogen-activated protein kinase (MAPK) cascades, cell cycle progression and transformation. In order to begin a study of TC10 biological function, we expressed wild type and various mutant forms of this protein in mammalian cells and investigated both the intracellular localization of the expressed proteins and their abilities to stimulate known Rho family-associated processes. Wild type TC10 was located predominantly in the cell membrane (apparently in the same regions as actin ®laments), GTPase defective (75L) and GTP-binding defective (31N) mutants were located predominantly in cytoplasmic perinuclear regions, and a deletion mutant lacking the carboxyl terminal residues required for posttranslational prenylation was located predominantly in the nucleus. The GTPase defective (constitutively active) TC10 mutant: (1) stimulated the formation of long ®lopodia; (2) activated c-Jun amino terminal kinase (JNK); (3) activated serum response factor (SRF)-dependent transcription; (4) activated NF-kB-dependent transcription; and (5) synergized with an activated Rafkinase (Raf-CAAX) to transform NIH3T3 cells. In addition, wild type TC10 function is required for full HRas transforming potential. We demonstrate that an intact e ector domain and carboxyl terminal prenylation signal are required for proper TC10 function and that TC10 signals to at least two separable downstream target pathways. In addition, TC10 interacted with the actin-binding and ®lament-forming protein, pro®lin, in both a two-hybrid cDNA library screen, and an in vitro binding assay. Taken together, these data support a classi®cation of TC10 as a member of the Rho family, and in particular, suggest that TC10 functions to regulate cellular signaling to the actin cytoskeleton and processes associated with cell growth.

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Section: Introductionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 97%

Section: Tc10 Binds Pro®lin a Mediator Of Actin ®Lament Formationmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 98%

See 3 more Smart Citations

Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth

Murphy

Solski²,

Jillian

et al. 1999

Oncogene

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The role of small GTPases in neuronal morphogenesis and polarity

et al. 2012

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The highly dynamic remodeling and cross talk of the microtubule and actin cytoskeleton support neuronal morphogenesis. Small RhoGTPases family members have emerged as crucial regulators of cytoskeletal dynamics. In this review we will comprehensively analyze findings that support the participation of RhoA, Rac, Cdc42, and TC10 in different neuronal morphogenetic events ranging from migration to synaptic plasticity. We will specifically address the contribution of these GTPases to support neuronal polarity and axonal elongation. V C 2012 Wiley Periodicals, Inc

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RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory ganglia, and corticospinal tract neurons and long‐lasting specific changes following spinal cord injury

Erschbamer

Hofstetter

Olson

2005

J of Comparative Neurology

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Inhibition of RhoA has been shown to enhance axonal regeneration following spinal cord injury. Here we mapped mRNA expression patterns of RhoA, B, and C, Rac1, Cdc42, and Tc10 in spinal cord, sensory ganglia, and sensorimotor cortex in uninjured rats, and following spinal cord injury or sham laminectomy. In the intact spinal cord, neurons displayed high levels of Rac1, Cdc42, and Tc10 mRNA hybridization signal. GFAP-immunoreactive astrocytes expressed primarily RhoB and Rac1, while oligodendrocyte-like cells expressed RhoA, Rac1, and Cdc42. Injury caused profound, long-lasting upregulation of RhoA, Rac1, Cdc42, and Tc10 mRNA in the spinal cord, while RhoB was modestly increased and RhoC did not change. GFAP-immunoreactive reactive astrocytes exhibited a dramatic increase of RhoA mRNA expression along with increases of Rac1 and Cdc42. Injury also led to elevation of RhoA, Cdc42, and Tc10 in neurons and modest increases of RhoA, Rac1, and Tc10 in oligodendrocyte-like cells. Laminectomy caused similar, but less pronounced alterations of investigated mRNA species. In dorsal root ganglia neuronal RhoA, Rac1, Cdc42, and Tc10 mRNA levels were increased similarly by spinal cord injury and sham surgery. The CST pyramidal cells expressed Tc10 mRNA and the CST itself was Tc10-immunoreactive. Tc10-immunoreactivity disappeared distal to injury. We conclude that there are gene-specific patterns of expression of the six different Rho-GTPases in normal spinal cord and dorsal root ganglia, and that specific changes of temporal and spatial expression patterns occur in response to spinal cord injury, suggesting different roles of these GTPases in the cellular sequelae of CNS injury.

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Distinct cellular effects and interactions of the Rho-family GTPase TC10

Abstract: TC10 possesses distinct features, but exhibits a phenotype most closely related to that of Cdc42. It interacts with a similar subset of effectors to Cdc42 but not with MLK3, WASP or ACK-1. It is regulated differentially by p50RhoGAP.

Cited by 127 publications

References 41 publications

Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth

Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth

The role of small GTPases in neuronal morphogenesis and polarity

RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory ganglia, and corticospinal tract neurons and long‐lasting specific changes following spinal cord injury

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