scholarly journals Overexpression of a Neural-specific Rho Family GTPase, cRac1B, Selectively Induces Enhanced Neuritogenesis and Neurite Branching in Primary Neurons

1998 ◽  
Vol 142 (3) ◽  
pp. 815-825 ◽  
Author(s):  
Chiara Albertinazzi ◽  
Daniela Gilardelli ◽  
Simona Paris ◽  
Renato Longhi ◽  
Ivan de Curtis
Keyword(s):  
Neural Development ◽  
Neuronal Morphology ◽  
Primary Neurons ◽  
Actin Organization ◽  
Inactive Form ◽  
Rho Family Gtpases ◽  
Neurite Formation ◽  
New Gene ◽  
Rho Family

Rho family GTPases have been implicated in cytoskeletal reorganization during neuritogenesis. We have recently identified a new gene of this family, cRac1B, specifically expressed in the chicken developing nervous system. This GTPase was overexpressed in primary neurons to study the role of cRac1B in the development of the neuronal phenotype. Overexpression of cRac1B induced an increment in the number of neurites per neuron, and dramatically increased neurite branching, whereas overexpression of the highly related and ubiquitous cRac1A GTPase did not evidently affect neuronal morphology. Furthermore, expression of an inactive form of cRac1B strikingly inhibited neurite formation. The specificity of cRac1B action observed in neurons was not observed in fibroblasts, where both GTPases produced similar effects on cell morphology and actin organization, indicating the existence of a cell type-dependent specificity of cRac1B function. Molecular dissection of cRac1B function by analysis of the effects of chimeric cRac1A/cRac1B proteins showed that the COOH-terminal portion of cRac1B is essential to induce increased neuritogenesis and neurite branching. Considering the distinctive regulation of cRac1B expression during neural development, our data strongly support an important role of cRac1B during neuritogenesis, and they uncover new mechanisms underlying the functional specificity of distinct Rho family GTPases.

The role of Rho-family GTPases in human glioblastomas

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
S Seta ◽  
M Herr ◽  
S Horn ◽  
D Koch ◽  
T Vogt ◽  
...  
Keyword(s):  
Rho Family Gtpases ◽  
Rho Family

scholarly journals Yeast Cdc42 functions at a late step in exocytosis, specifically during polarized growth of the emerging bud

2001 ◽  
Vol 155 (4) ◽  
pp. 581-592 ◽  
Author(s):  
Joan E. Adamo ◽  
John J. Moskow ◽  
Amy S. Gladfelter ◽  
Domenic Viterbo ◽  
Daniel J. Lew ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Temperature Sensitive ◽  
Secretory Vesicles ◽  
Polarized Growth ◽  
Vesicle Docking ◽  
Actin Organization ◽  
Late Step ◽  
Rho Family ◽  
Localization Data

The Rho family GTPase Cdc42 is a key regulator of cell polarity and cytoskeletal organization in eukaryotic cells. In yeast, the role of Cdc42 in polarization of cell growth includes polarization of the actin cytoskeleton, which delivers secretory vesicles to growth sites at the plasma membrane. We now describe a novel temperature-sensitive mutant, cdc42-6, that reveals a role for Cdc42 in docking and fusion of secretory vesicles that is independent of its role in actin polarization. cdc42-6 mutants can polarize actin and deliver secretory vesicles to the bud, but fail to fuse those vesicles with the plasma membrane. This defect is manifested only during the early stages of bud formation when growth is most highly polarized, and appears to reflect a requirement for Cdc42 to maintain maximally active exocytic machinery at sites of high vesicle throughput. Extensive genetic interactions between cdc42-6 and mutations in exocytic components support this hypothesis, and indicate a functional overlap with Rho3, which also regulates both actin organization and exocytosis. Localization data suggest that the defect in cdc42-6 cells is not at the level of the localization of the exocytic apparatus. Rather, we suggest that Cdc42 acts as an allosteric regulator of the vesicle docking and fusion apparatus to provide maximal function at sites of polarized growth.

Regulation of class IA PI3Ks

2007 ◽  
Vol 35 (2) ◽  
pp. 242-244 ◽  
Author(s):  
H. Wu ◽  
Y. Yan ◽  
J.M. Backer
Keyword(s):  
Tyrosine Kinases ◽  
Regulatory Subunit ◽  
Sh2 Domains ◽  
Src Homology 2 ◽  
Pi3k Activity ◽  
Wide Range ◽  
Rho Family Gtpases ◽  
Src Homology ◽  
Rho Family

Class IA PI3Ks (phosphoinositide 3-kinases) regulate a wide range of cellular responses through the production of PI(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate) in cellular membranes. They are activated by receptor tyrosine kinases, by Ras and Rho family GTPases, and in some cases by Gβγ subunits from trimeric G-proteins. Crystallographic studies on the related class IB PI3Kγ, and biochemical and structural studies on the class IA PI3Ks, have led to new insights into how these critical enzymes are regulated in normal cells and how mutations can lead to their constitutive activation in transformed cells. The present paper will discuss recent studies on the regulation of class I (p85/p110) PI3Ks, with a focus on the role of SH2 domains (Src homology 2 domains) in the p85 regulatory subunit in modulating PI3K activity.

scholarly journals Microtubule Dynamics and Neuronal Excitability: Advances on Cytoskeletal Components Implicated in Epileptic Phenomena

2020 ◽  
Author(s):  
Giuditta Gambino ◽  
Valerio Rizzo ◽  
Giuseppe Giglia ◽  
Giuseppe Ferraro ◽  
Pierangelo Sardo
Keyword(s):  
Neuronal Network ◽  
Neural Development ◽  
Neuronal Excitability ◽  
Neuronal Morphology ◽  
Microtubule Dynamics ◽  
Limited Attention ◽  
Potential Implication ◽  
Associated Proteins ◽  
Epilepsy Models

Abstract Extensive researches have deepened knowledge on the role of synaptic components in epileptogenesis, but limited attention has been devoted to the potential implication of the cytoskeleton. The study of the development of epilepsy and hyperexcitability states involves molecular, synaptic, and structural alterations of neuronal bioelectric activity. In this paper we aim to explore the neurobiological targets involved in microtubule functioning and cytoskeletal transport, i.e. how dynamic scaffolding of microtubules can influence neuronal morphology and excitability, in order to suggest a potential role for microtubule dynamics in the processes turning a normal neuronal network in a hyperexcited one. Pathophysiological alterations of microtubule dynamics inducing neurodegeneration, network remodeling and relative impairment on synaptic transmission were overviewed. Recent researches were reported on the phosphorylation state of microtubule-associated proteins such as tau in neurodegenerative diseases and epileptic states, but also on the effect of microtubule-active agents influencing cytoskeleton destabilization in epilepsy models. The manipulation of microtubule polymerization was found effective in the modulation of hyperexcitability. In addition, it was considered the importance of microtubules and related neurotrophic factors during neural development since they are essential for the formation of a properly functional neuronal network. Otherwise, this can lead to cognitive deficits, hyperexcitability phenomena and neurodevelopmental disorders. Lastly, we evaluated the role of microtubule dynamics on neuronal efficiency considering their importance in the transport of mitochondria, cellular elements fulfilling energy requirements for neuronal activity, and a putative influence on cannabinoid-mediated neuroprotection. This review provides novel perspectives for the implication of microtubule dynamics in the development of epileptic phenomena.

scholarly journals Induction of filopodia-like protrusions by transmembrane agrin: Role of agrin glycosaminoglycan chains and Rho-family GTPases

2010 ◽  
Vol 316 (14) ◽  
pp. 2260-2277 ◽  
Author(s):  
Lin Lin ◽  
Seumas McCroskery ◽  
Jaime M. Ross ◽  
Yvonne Chak ◽  
Birgit Neuhuber ◽  
...  
Keyword(s):  
Rho Family Gtpases ◽  
Rho Family

Desensitization of the PDGFβ Receptor by Modulation of the Cytoskeleton: The Role of p21Ras and Rho Family GTPases

2002 ◽  
Vol 275 (1) ◽  
pp. 17-30 ◽  
Author(s):  
Ligaya L. Stice ◽  
Lora W. Forman ◽  
Chang S. Hahn ◽  
Douglas V. Faller
Keyword(s):  
Rho Family Gtpases ◽  
Rho Family

scholarly journals The integrin cytoplasmic domain-associated protein ICAP-1 binds and regulates Rho family GTPases during cell spreading

2002 ◽  
Vol 156 (2) ◽  
pp. 377-388 ◽  
Author(s):  
Simona Degani ◽  
Fiorella Balzac ◽  
Mara Brancaccio ◽  
Simona Guazzone ◽  
Saverio Francesco Retta ◽  
...  
Keyword(s):  
Cell Spreading ◽  
Cytoplasmic Domain ◽  
Nih3t3 Cells ◽  
Cell Matrix ◽  
Rho Family Gtpases ◽  
Rho Family ◽  
First Time ◽  
Cell Matrix Adhesion

Using two-hybrid screening, we isolated the integrin cytoplasmic domain-associated protein (ICAP-1), an interactor for the COOH terminal region of the β1A integrin cytoplasmic domain. To investigate the role of ICAP-1 in integrin-mediated adhesive function, we expressed the full-length molecule in NIH3T3 cells. ICAP-1 expression strongly prevents NIH3T3 cell spreading on extracellular matrix. This inhibition is transient and can be counteracted by coexpression of a constitutively activated mutant of Cdc42, suggesting that ICAP-1 acts upstream of this GTPase. In addition, we found that ICAP-1 binds both to Cdc42 and Rac1 in vitro, and its expression markedly inhibits activation of these GTPases during integrin-mediated cell adhesion to fibronectin as detected by PAK binding assay. In the attempt to define the molecular mechanism of this inhibition, we show that ICAP-1 reduces both the intrinsic and the exchange factor–induced dissociation of GDP from Cdc42; moreover, purified ICAP-1 displaces this GTPase from cellular membranes. Together, these data show for the first time that ICAP-1 regulates Rho family GTPases during integrin-mediated cell matrix adhesion, acting as guanine dissociation inhibitor.

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