Signaling networks of Rho GTPases in cell motility

Hanna, Samer; El‐Sibai, Mirvat

doi:10.1016/j.cellsig.2013.04.009

Cited by 233 publications

(205 citation statements)

References 82 publications

Supporting

Mentioning

192

Contrasting

Unclassified

Order By: Relevance

“…57,58 Normal fibroblasts have a rather impressive actin filament network. Exploring the effect of RhoB depletion on the cytoskeleton by transducing HFFs with the lentiviral vector, TRIPZshRhoB, we observed a robust modification in the alignment of stress fibers, from the parallel-running actin fibers in the normal fibroblasts (Fig.…”

Section: Depletion Of Rhob Results In Reduction Of Progeny Virion Promentioning

confidence: 99%

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

et al. 2015

View full text Add to dashboard Cite

Human Cytomegalovirus (HCMV), an ubiquitous b-herpesvirus, is a significant pathogen that causes medically severe diseases in immunocompromised individuals and in congenitally infected neonates. RhoB belongs to the family of Rho GTPases, which regulates diverse cellular processes. Rho proteins are implicated in the entry and egress from the host cell of mainly a-and g-herpesviruses, whereas b-herpesviruses are the least studied in this regard. Here, we studied the role of RhoB GTPase during HCMV lytic infection. Microscopy analysis, both in fixed and live infected cells showed that RhoB was translocated to the assembly complex/compartment (AC) of HCMV, a cytoplasmic zone in infected cells where many viral structural proteins are known to accumulate and assembly of new virions takes place. Furthermore, RhoB was localized at the AC even when the expression of the late HCMV AC proteins was inhibited. At the very late stages of infection, cellular projections were formed containing RhoB and HCMV virions, potentially contributing to the successful viral spread. Interestingly, the knockdown of RhoB in HCMV-infected cells resulted in a significant reduction of the virus titer and could also affect the accumulation of AC viral proteins at this subcellular compartment. RhoB knockdown also affected actin fibers' structure. Actin reorganization was observed at late stages of infection originating from the viral AC and surrounding the cellular projections, implying a potential interplay between RhoB and actin during HCMV assembly and egress. In conclusion, our results demonstrate for the first time that RhoB is a constituent of the viral AC and is required for HCMV productive infection.

show abstract

Section: Depletion Of Rhob Results In Reduction Of Progeny Virion Promentioning

confidence: 99%

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

et al. 2015

View full text Add to dashboard Cite

show abstract

“…RHOA is a member of the Rho family of small GTPases that links cell-surface receptors to different intracellular signaling proteins. In its active GTP-bound state, RHOA functions in controlling the actin cytoskeleton and stress fibers [122]. The most prominent mutation is RHOA G17V which acts as a dominant-negative molecule, underpinning its tumor-suppressive function in T-cells [93–95].…”

Section: Targets In Ptcl and Driver Mutationsmentioning

confidence: 99%

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Orlova

Wingelhofer

Neubauer

et al. 2017

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

Introduction: Hematopoietic neoplasms are often driven by gain-of-function mutations of the JAK-STAT pathway together with mutations in chromatin remodeling and DNA damage control pathways. The interconnection between the JAK-STAT pathway, epigenetic regulation or DNA damage control is still poorly understood in cancer cell biology. Areas covered: Here, we focus on a broader description of mutational insights into myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas, since sequencing efforts have identified similar combinations of driver mutations in these diseases covering different lineages. We summarize how these pathways might be interconnected in normal or cancer cells, which have lost differentiation capacity and drive oncogene transcription. Expert opinion: Due to similarities in driver mutations including epigenetic enzymes, JAK-STAT pathway activation and mutated checkpoint control through TP53, we hypothesize that similar therapeutic approaches could be of benefit in these diseases. We give an overview of how driver mutations in these malignancies contribute to hematopoietic cancer initiation or progression, and how these pathways can be targeted with currently available tools.

show abstract

“…However, previous studies in developing brains and in maturing neurons in culture provide valuable clues. Of particular interest is the Rho-family of guanosine triphosphatases (GTPases), a subfamily of the Ras superfamily of GTPases, which stimulate a wide array of cellular processes, including morphogenesis, cell migration, mitosis, and adhesion [21][22][23]. The Rho subfamily is further divided into 7 subfamilies (Rho, Rac, Cdc42, Rnd, RhoD, RhoBTB, and RhoH), of which the most extensively studied members are RhoA, Rac1, and Cdc42 for their role in regulating the actin cytoskeleton, the main structural component of dendritic spines, and thus in controlling spine dynamics [24][25][26][27].…”

Section: Rho-guanosine Triphosphatases At the Center Of Ad Pathologymentioning

confidence: 99%

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

Lefort

2015

Neurotherapeutics

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a monumental public health crisis with no effective cure or treatment. To date, therapeutic strategies have focused almost exclusively on upstream signaling events in the disease, namely on β-amyloid and amyloid precursor protein processing, and have, unfortunately, yielded few, if any, promising results. An alternative approach may be to target signaling events downstream of β-amyloid and even tau. However, with so many pathways already linked to the disease, understanding which ones are "drivers" versus "passengers" in the pathogenesis of the disease remains a tremendous challenge. Given the critical roles of Rho-guanosine triphosphatases (GTPases) in regulating the actin cytoskeleton and spine dynamics, and the strong association between spine abnormalities and cognition, it is not surprising that mutations in a number of genes involved in RhoGTPase signaling have been implicated in several brain disorders, including schizophrenia and autism. And now, there is mounting literature implicating Rho-GTPase signaling in AD pathogenesis as well. Here, I review this evidence, with a particular emphasis on the regulators of Rho-GTPase signaling, namely guanine nucleotide exchange factors and GTPaseactivating proteins. Several of these have been linked to various aspects of AD, and each offers a novel potential therapeutic target for AD.

show abstract

Signaling networks of Rho GTPases in cell motility

Cited by 233 publications

References 82 publications

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

Emerging therapeutic targets in myeloproliferative neoplasms and peripheral T-cell leukemia and lymphomas

Reversing Synapse Loss in Alzheimer's Disease: Rho-Guanosine Triphosphatases and Insights from Other Brain Disorders

Contact Info

Product

Resources

About