ArticlePloS one2010
The RhoA GEF Syx is a target of Rnd3 and regulated via a Raf1-like ubiquitin-related domain.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Identification and characterization of a new isoform of small GTPase RhoE.Communications biology · 2020Article
- The RND1 Small GTPase: Main Functions and Emerging Role in Oncogenesis.International journal of molecular sciences · 2019Review
- Activated Rho GTPases in Cancer-The Beginning of a New Paradigm.International journal of molecular sciences · 2018Review
- A Rnd3/p190RhoGAP pathway regulates RhoA activity in idiopathic pulmonary fibrosis fibroblasts.Molecular biology of the cell · 2018Article
- Sema3d controls collective endothelial cell migration by distinct mechanisms via Nrp1 and PlxnD1.The Journal of cell biology · 2016Article
- RND1 is up-regulated in esophageal squamous cell carcinoma and promotes the growth and migration of cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Pathophysiological Functions of Rnd3/RhoE.Comprehensive Physiology · 2015Review
- Function and regulation of Rnd proteins in cortical projection neuron migration.Frontiers in neuroscience · 2015Review
- Ras GTPases' interaction with effector domains: Breaking the families' barrier.Communicative & integrative biology · 2013Article
- RAF1-MEK1-ERK/AKT axis may confer NSCLC cell lines resistance to erlotinib.International journal of clinical and experimental pathology · 2013Article
- A genome-wide screen of CREB occupancy identifies the RhoA inhibitors Par6C and Rnd3 as regulators of BDNF-induced synaptogenesis.PloS one · 2013Article
- The GTPase-deficient Rnd proteins are stabilized by their effectors.The Journal of biological chemistry · 2012Article
- RHGF-2 is an essential Rho-1 specific RhoGEF that binds to the multi-PDZ domain scaffold protein MPZ-1 in Caenorhabditis elegans.PloS one · 2012Article
- RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice.PloS one · 2011Article
- p53 and its mutants in tumor cell migration and invasion.The Journal of cell biology · 2011Review
- Pathophysiological functions of Rnd proteins.Small GTPasesReview
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRnd3 (RhoE) protein belongs to the unique branch of Rho family GTPases that has low intrinsic GTPase activity and consequently remains constitutively active [1], [2]. The current consensus is that Rnd1 and Rnd3 function as important antagonists of RhoA signaling primarily by activating the ubiquitous p190 RhoGAP [3], but not by inhibiting the ROCK family kinases. METHODOLOGY/PRINCIPAL
findingsRnd3 is abundant in mouse embryonic stem (mES) cells and in an unbiased two-step affinity purification screen we identified a new Rnd3 target, termed synectin-binding RhoA exchange factor (Syx), by mass spectrometry. The Syx interaction with Rnd3 does not occur through the Syx DH domain but utilizes a region similar to the classic Raf1 Ras-binding domain (RBD), and most closely related to those in RGS12 and RGS14. We show that Syx behaves as a genuine effector of Rnd3 (and perhaps Rnd1), with binding characteristics similar to p190-RhoGAP. Morpholino-oligonucleotide knockdown of Syx in zebrafish at the one cell stage resulted in embryos with shortened anterior-posterior body axis: this phenotype was effectively rescued by introducing mouse Syx1b mRNA. A Rnd3-binding defective mutant of Syx1b mutated in the RBD (E164A/R165D) was more potent in rescuing the embryonic defects than wild-type Syx1b, showing that Rnd3 negatively regulates Syx activity in vivo. CONCLUSIONS/SIGNIFICANCE: This study uncovers a well defined Rnd3 effector Syx which is widely expressed and directly impacts RhoA activation. Experiments conducted in vivo indicate that Rnd3 negatively regulates Syx, and that as a RhoA-GEF it plays a key role in early embryonic cell shape changes. Thus a connection to signaling via the planar cell polarity pathway is suggested.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.