The Ras family G-proteins RalA and RalB make critical non-overlapping contributions to the generation of a tumorigenic regulatory network, supporting bypass of the normal restraints on both cell proliferation and survival. The Sec6/8 complex, or exocyst, has emerged as a principal direct effector complex for Ral GTPases. Here, we show that RalA and RalB support mitotic progression through mobilization of the exocyst for two spatially and kinetically distinct steps of cytokinesis. RalA is required to tether the exocyst to the cytokinetic furrow in early cytokinesis. RalB is then required for recruitment of the exocyst to the midbody of this bridge to drive abscission and completion of cytokinesis. The collaborative action of RalA and RalB is specified by discrete subcellular compartmentalization and unique pairs of RalGEF proteins that provide inputs from both Ras-family protein-dependent and protein-independent regulatory cues. This suggests that Ral GTPases integrate diverse upstream signals to choreograph multiple roles for the exocyst in mitotic progression.
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http://dx.doi.org/10.1038/emboj.2008.166 | DOI Listing |
Ageing Res Rev
January 2025
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Nutritional Sciences Department, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, United States; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA 5. Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Speech, Language, and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address:
J Thromb Haemost
January 2025
School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, United Kingdom. Electronic address:
Background: Deep vein thrombosis is a major cause of morbidity and mortality globally. While its pathophysiology is complex, increasing evidence suggests a more prominent role for platelets than previously suspected. Genetic deletion of Ral GTPases, RalA and RalB, conditionally in mouse platelets (RalAB double knockout [DKO]), results in a near complete defect in P-selectin externalization upon activation, while other platelet activation responses and arterial thrombosis are preserved.
View Article and Find Full Text PDFInt J Mol Sci
September 2024
Department of Ophthalmology, Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School, Boston, MA 02114, USA.
Communication between the different layers of the cornea (epithelium and stroma) is a complex, yet crucial element in the corneal healing process. Upon corneal injury, it has been reported that the bi-directional cross talk between the epithelium and stroma via the vesicular secretome, namely, extracellular vesicles (EVs), can lead to accelerated wound closure upon injury. However, the distinct protein markers of EVs derived from human corneal epithelial (HCE) cells, keratocytes (HCKs), fibroblasts (HCFs), and myofibroblasts (HCMs) remain poorly understood.
View Article and Find Full Text PDFCancers (Basel)
August 2024
Department of Radiation Oncology, Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Breast cancer (BC) is the most frequent cancer and second-leading cause of cancer deaths in women in the United States. While RAS mutations are infrequent in BC, triple-negative (TN) and HER2-positive (HER2+) BC both exhibit increased RAS activity. Here, we tested the RAS effectors RALA and RALB, which are overexpressed in BC, as tractable molecular targets in these subtypes.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2024
Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL 61801.
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