Rho GTPases and their role in organizing the actin cytoskeleton

Sit, Soon-Tuck; Manser, Ed

doi:10.1242/jcs.064964

Cited by 436 publications

(406 citation statements)

References 93 publications

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“…Our data also show that Gef1 removal depends on the presence of actin cables and the formin For3. Actin cytoskeleton organization is primarily regulated by Cdc42 (Sit and Manser, 2011). We find that scd1Δ mutants show depolarized actin cables and patches likely due to mis-regulation of Cdc42.…”

Section: Crosstalk Between Gef1 and Scd1 During Cytokinesismentioning

confidence: 69%

A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis

Hercyk

Rich

Das

2018

Preprint

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Cdc42, a conserved regulator of cell polarity, is activated by two GEFs, Gef1 and Scd1, in fission yeast. While gef1 and scd1 mutants exhibit distinct phenotypes, how they do so is unclear given that they activate the same GTPase. Using the GEF localization pattern during cytokinesis as a paradigm, we report a novel interplay between Gef1 and Scd1 that spatially modulates Cdc42. We find that Gef1 promotes Scd1 localization to the division site during cytokinesis and to the new end during polarized growth through the recruitment of the scaffold Scd2 via a Cdc42 feedforward pathway. Gef1-mediated Scd1 recruitment at the new end enables the transition from monopolar to bipolar growth. Reciprocally, Scd1 restricts Gef1 localization to prevent ectopic Cdc42 activation during cytokinesis to promote cell separation and during interphase to maintain cell shape. Our findings reveal an elegant regulatory pattern in which Gef1 establishes new sites of Scd1-mediated Cdc42 activity, while Scd1 restricts Gef1 to functional sites. We propose that crosstalk between GEFs is a conserved mechanism that orchestrates Cdc42 activation during complex cellular processes.Summary StatementCdc42 GEFs Gef1 and Scd1 crosstalk to fine-tune Cdc42 activity. This crosstalk promotes bipolar growth and maintains cell shape in fission yeast.

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Section: Crosstalk Between Gef1 and Scd1 During Cytokinesismentioning

confidence: 69%

A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis

Hercyk

Rich

Das

2018

Preprint

View full text Add to dashboard Cite

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“…We therefore investigated other pathways implicated in RhoA/ROCK signaling that may also affect NMII localization. The actin cytoskeleton being the most important effector of the RhoA/ROCK pathway, 22 we investigated actin dynamics at the cleavage furrow of megakaryocytes and erythroblasts. Increased actin turnover was observed at the megakaryocyte cleavage furrow when compared with erythroblasts.…”

Section: Discussionmentioning

confidence: 99%

Activity of nonmuscle myosin II isoforms determines localization at the cleavage furrow of megakaryocytes

Roy

Lordier

Mazzi

et al. 2016

Blood

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Key Points• RhoA-dependent differential activity of NMII isoforms determines its localization at the cleavage furrow of megakaryocytes.• Perturbation of the actin cytoskeleton was sufficient to induce the differential localization of NMII isoforms.Megakaryocyte polyploidy is characterized by cytokinesis failure resulting from defects in contractile forces at the cleavage furrow. Although immature megakaryocytes express 2 nonmuscle myosin II isoforms (MYH9 [NMIIA] and MYH10 [NMIIB]), only NMIIB localizes at the cleavage furrow, and its subsequent absence contributes to polyploidy. In this study, we tried to understand why the abundant NMIIA does not localize at the furrow by focusing on the RhoA/ROCK pathway that has a low activity in polyploid megakaryocytes. We observed that under low RhoA activity, NMII isoforms presented different activity that determined their localization. Inhibition of RhoA/ROCK signaling abolished the localization of NMIIB, whereas constitutively active RhoA induced NMIIA at the cleavage furrow. Thus, although high RhoA activity favored the localization of both the isoforms, only NMIIB could localize at the furrow at low RhoA activity. This was further confirmed in erythroblasts that have a higher basal RhoA activity than megakaryocytes and express both NMIIA and NMIIB at the cleavage furrow. Decreased RhoA activity in erythroblasts abolished localization of NMIIA but not of NMIIB from the furrow. This differential localization was related to differences in actin turnover. Megakaryocytes had a higher actin turnover compared with erythroblasts. Strikingly, inhibition of actin polymerization was found to be sufficient to recapitulate the effects of inhibition of RhoA/ROCK pathway on NMII isoform localization; thus, cytokinesis failure in megakaryocytes is the consequence of both the absence of NMIIB and a low RhoA activity that impairs NMIIA localization at the cleavage furrow through increased actin turnover. (Blood. 2016;128(26):3137-3145)

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“…(31,(36)(37)(38)(39)(40)(41)(42)(43). Furthermore, inhibition of Rho, a small GTPase protein involved in actin polymerization (44), results in AQP2 membrane localization (36,38,42,45). Activation of Rho by bradykinin, a peptide hormone that reduces vasopressin-induced water permeability in isolated, perfused collecting ducts (46), promotes actin polymerization, and inhibits apical AQP2 localization (47).…”

Section: Discussionmentioning

confidence: 99%

Quantitative apical membrane proteomics reveals vasopressin-induced actin dynamics in collecting duct cells

Loo

Chen

Wang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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In kidney collecting duct cells, filamentous actin (F-actin) depolymerization is a critical step in vasopressin-induced trafficking of aquaporin-2 to the apical plasma membrane. However, the molecular components of this response are largely unknown. Using stable isotope-based quantitative protein mass spectrometry and surface biotinylation, we identified 100 proteins that showed significant abundance changes in the apical plasma membrane of mouse cortical collecting duct cells in response to vasopressin. Fourteen of these proteins are involved in actin cytoskeleton regulation, including actin itself, 10 actin-associated proteins, and 3 regulatory proteins. Identified were two integral membrane proteins (Clmn, Nckap1) and one actin-binding protein (Mpp5) that link F-actin to the plasma membrane, five F-actin end-binding proteins (Arpc2, Arpc4, Gsn, Scin, and Capzb) involved in F-actin reorganization, and two actin adaptor proteins (Dbn1, Lasp1) that regulate actin cytoskeleton organization. There were also protease (Capn1), protein kinase (Cdc42bpb), and Rho guanine nucleotide exchange factor 2 (Arhgef2) that mediate signal-induced F-actin changes. Based on these findings, we devised a live-cell imaging method to observe vasopressininduced F-actin dynamics in polarized mouse cortical collecting duct cells. In response to vasopressin, F-actin gradually disappeared near the center of the apical plasma membrane while consolidating laterally near the tight junction. This F-actin peripheralization was blocked by calcium ion chelation. Vasopressin-induced apical aquaporin-2 trafficking and forskolin-induced water permeability increase were blocked by F-actin disruption. In conclusion, we identified a vasopressin-regulated actin network potentially responsible for vasopressin-induced apical F-actin dynamics that could explain regulation of apical aquaporin-2 trafficking and water permeability increase.V asopressin regulates aquaporin-2 (AQP2) and osmotic water transport in the collecting duct by regulating total AQP2 protein abundance and AQP2 trafficking to and from the apical plasma membrane of principal cells (1). Understanding these regulatory mechanisms at the molecular level is important to the ultimate understanding of the pathophysiology of multiple water balance disorders (2). This goal is abetted by the methods of molecular systems biology (proteomics and transcriptomics), which not only reveal "parts lists" for collecting duct cells but also can identify what biological and molecular processes are regulated by vasopressin. These proteomic and transcriptomic data have been made publicly available in databases (3). Many of these studies have focused on whole cells (4-6), whereas several analyzed subcellular fractions (7-12). Analysis of subcellular fractions is technically demanding, but it has the benefit of identifying low abundance proteins with important functions. To identify proteins potentially involved in apical AQP2 trafficking, we previously used NHS-based surface biotinylation coupled to streptavidin...

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Rho GTPases and their role in organizing the actin cytoskeleton

Cited by 436 publications

References 93 publications

A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis

A novel interplay between GEFs orchestrates Cdc42 activity during cell polarity and cytokinesis

Activity of nonmuscle myosin II isoforms determines localization at the cleavage furrow of megakaryocytes

Quantitative apical membrane proteomics reveals vasopressin-induced actin dynamics in collecting duct cells

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