The RGK family of proteins, small GTPases of the Ras superfamily, are known to regulate calcium currents. It is commonly thought that this is due to an interaction with the Cavβ subunit, however, the mechanism of this inhibition is unclear. There have been conflicting reports of whether RGK proteins can affect channel trafficking or whether they reduce calcium currents by interacting with channels at the membrane. In the last year, several studies have emerged which explore the intricacies of RGK protein interaction with the channel itself and the importance of the Cavβ subunit for this interaction, in addition to providing some tantalizing suggestions for the mechanism by which RGK proteins reduce or eliminate calcium currents. In this review, we present an overview of these recent advances and suggest a model that may synthesize these latest works.
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http://dx.doi.org/10.4161/chan.4.6.12865 | DOI Listing |
N Engl J Med
January 2025
From the TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston (C.T.R., S.M.P., R.P.G., D.A.M., J.F.K., E.L.G., S.A.M., S.D.W., M.S.S.); Anthos Therapeutics, Cambridge, MA (B.H., S.P., D.B.); the Heart Rhythm Center, Taipei Veterans General Hospital and Cardiovascular Center, Taipei, Taiwan (S.-A.C.); Taichung Veterans Hospital, Taichung, Taiwan (S.-A.C.); National Yang Ming Chiao Tung University, Hsinchu, Taiwan (S.-A.C.); National Chung Hsing University, Taichung, Taiwan (S.-A.C.); St. Michael's Hospital, Unity Health Toronto, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto (S.G.G.); Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.); the Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea (B.J.); the Department of Cardiology, Central Hospital of Northern Pest-Military Hospital, Budapest, Hungary (R.G.K.); the Heart and Vascular Center, Semmelweis University, Budapest, Hungary (R.G.K.); the Internal Cardiology Department, St. Ann University Hospital and Masaryk University, Brno, Czech Republic (J.S.); the Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland (W.W.); the Departments of Medicine and of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada (J.W.); and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada (J.W.).
Background: Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown.
Methods: Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion.
Diabetologia
January 2025
Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
Aims/hypothesis: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by enteroendocrine K cells in the proximal small intestine. This study aimed to explore the function of human K cells at the molecular and cellular levels.
Methods: CRISPR-Cas9 homology-directed repair was used to insert transgenes encoding a yellow fluorescent protein (Venus) or an Epac-based cAMP sensor (Epac-S-H187) in the GIP locus in human duodenal-derived organoids.
Gastroenterology
December 2024
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:
Background & Aims: Inflammatory bowel disease (IBD) is a chronic manifestation of dysregulated immune response to the gut microbiota in genetically predisposed hosts. Nearly half of patients with Crohn's disease (CD) develop selective serum immunoglobulin (Ig)G response to flagellin proteins expressed by bacteria in the Lachnospiraceae family. This study aimed to identify the binding epitopes of these IgG antibodies and assess their relevance in CD and in homeostasis.
View Article and Find Full Text PDFFront Bioinform
June 2024
Department of Biology, Temple University, Philadelphia, PA, United States.
Rad And Gem-Like GTP-Binding Protein 2 (Rem2), a member of the RGK family of Ras-like GTPases, is implicated in Huntington's disease and Long QT Syndrome and is highly expressed in the brain and endocrine cells. We examine the evolutionary history of Rem2 identified in various mammalian species, focusing on the role of purifying selection and coevolution in shaping its sequence and protein structural constraints. Our analysis of Rem2 sequences across 175 mammalian species found evidence for strong purifying selection in 70% of non-invariant codon sites which is characteristic of essential proteins that play critical roles in biological processes and is consistent with Rem2's role in the regulation of neuronal development and function.
View Article and Find Full Text PDFJ Clin Invest
January 2024
Division of Cardiology, Department of Medicine, and.
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