Divergence of Rho residue 43 impacts GEF activity

Sloan, Christina M.; Quinn, Clancy V.; Peters, Justin P.; Farley, Janean; Goetzinger, Chris; Wernli, Molly; DeMali, Kris A.; Ellerbroek, Shawn M.

doi:10.4161/sgtp.19557

Cited by 8 publications

(5 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A bulkier isoleucine residue at this point could sterically block the interaction between the RhoGTPase and its GEF. Indeed, the GEF XPLN interacts with RhoA and RhoB but not RhoC, the distinguishing feature being the isoleucine residue at position 43 in RhoC ( Arthur et al., 2002 , Sloan et al., 2012 ). Conversely, it is also conceivable that RhoD/Pak6 can activate a GAP capable of downregulating RhoC signaling.…”

Section: Discussionmentioning

confidence: 99%

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

et al. 2017

View full text Add to dashboard Cite

SummaryRhoA-mediated regulation of myosin-II activity in the actin cortex controls the ability of cells to contract and bleb during a variety of cellular processes, including cell migration and division. Cell contraction and blebbing also frequently occur as part of the cytopathic effect seen during many different viral infections. We now demonstrate that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from 2 hr post infection. Curiously, F11-induced cell contraction is dependent on RhoC and not RhoA signaling to ROCK. Moreover, RhoC-driven cell contraction depends on the upstream inhibition of RhoD signaling by F11. This inhibition prevents RhoD from regulating its downstream effector Pak6, alleviating the suppression of RhoC by the kinase. Our observations with vaccinia have now demonstrated that RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing.

show abstract

Section: Discussionmentioning

confidence: 99%

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

et al. 2017

View full text Add to dashboard Cite

show abstract

“…RhoGEFs that show isoform specificity among RhoA, RhoB, and RhoC are very rare. One example is XPLN, which shows activity toward RhoA and RhoB but not RhoC due to an amino acid difference (Ile43 vs. Val43) at the N-terminus of the Rho isoforms [20,21]. Another example is SmgGDS, which specifically activates RhoA and RhoC but not RhoB [22].…”

Section: Gdp/gtp Cyclingmentioning

confidence: 99%

RhoA Signaling in Neurodegenerative Diseases

Schmidt

Blaabjerg

Freude

et al. 2022

Cells

View full text Add to dashboard Cite

Ras homolog gene family member A (RhoA) is a small GTPase of the Rho family involved in regulating multiple signal transduction pathways that influence a diverse range of cellular functions. RhoA and many of its downstream effector proteins are highly expressed in the nervous system, implying an important role for RhoA signaling in neurons and glial cells. Indeed, emerging evidence points toward a role of aberrant RhoA signaling in neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. In this review, we summarize the current knowledge of RhoA regulation and downstream cellular functions with an emphasis on the role of RhoA signaling in neurodegenerative diseases and the therapeutic potential of RhoA inhibition in neurodegeneration.

show abstract

“…1 and 2A-F). 29,30 Although the structure of the complex of Rho and XPLN has not been resolved yet, it has been suggested that Ile43 in RhoC, which has a slightly bulkier side chain than Val43 in RhoA and RhoB, interferes with the binding and activity of XPLN ( Fig. 2D-F).…”

Section: Rhogefsmentioning

confidence: 99%

Toward understanding RhoGTPase specificity: structure, function and local activation

2014

View full text Add to dashboard Cite

Cell adhesion and migration are regulated through the concerted action of cytoskeletal dynamics and adhesion proteins, the activity of which is governed by RhoGTPases. Specific RhoGTPase signaling requires spatio-temporal activation and coordination of subsequent protein-protein and protein-lipid interactions. The nature, location and duration of these interactions are dependent on polarized extracellular triggers, such as cell-cell contact, and intracellular modifying events, such as phosphorylation. RhoA, RhoB, and RhoC are highly homologous GTPases that, however, succeed in generating specific intracellular responses. Here, we discuss the key features that contribute to this specificity. These not only include the well-studied switch regions, the conformation of which is nucleotide-dependent, but also additional regions and seemingly small differences in primary sequence that also contribute to specific interactions. These differences translate into differential surface charge distribution, local exposure of amino acid side-chains and isoform-specific post-translational modifications. The available evidence supports the notion that multiple regions in RhoA/B/C cooperate to provide specificity in binding to regulators and effectors. These specific interactions are highly regulated in time and space. We therefore subsequently discuss current approaches means to visualize and analyze localized GTPase activation using biosensors that allow imaging of isoform-specific, localized regulation.

show abstract

Divergence of Rho residue 43 impacts GEF activity

Cited by 8 publications

References 35 publications

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

RhoA Signaling in Neurodegenerative Diseases

Toward understanding RhoGTPase specificity: structure, function and local activation

Contact Info

Product

Resources

About