Certain types of intracellular organelle transport to the cell periphery are thought to involve long-range movement on microtubules by kinesin with subsequent handoff to vertebrate myosin Va (myoVa) for local delivery on actin tracks. This process may involve direct interactions between these two processive motors. Here we demonstrate using single molecule in vitro techniques that myoVa is flexible enough to effectively maneuver its way through actin filament intersections and Arp2/3 branches. In addition, myoVa surprisingly undergoes a one-dimensional diffusive search along microtubules, which may allow it to scan efficiently for kinesin and/or its cargo. These features of myoVa may help ensure efficient cargo delivery from the cell center to the periphery.
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| http://dx.doi.org/10.1073/pnas.0611471104 | DOI Listing |
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View Article and Find Full Text PDFAficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.
N Engl J Med
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From Lahey Hospital and Medical Center, Burlington (M.S.M.), and the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School (B.C., S.D.S.), the Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School (J.L.J., G.D.L.), and the Baim Institute for Clinical Research (J.L.J.), Boston - all in Massachusetts; Oregon Health and Science University, Portland (A.M.); the University of Missouri Kansas City Healthcare Institute for Innovations in Quality and Saint Luke's Mid America Heart Institute, Kansas City (M.E.N., J.A.S.); Complejo Hospitalario Universitario de A Coruña, Instituto de Investigación Biomédica de A Coruña, Centro de Investigación Biomédica en Red de Enfermedades Cardiovaculares (CIBERCV)-Instituto de Salud Carlos III, A Coruña (R.B.-V.), and Hospital Universitario Puerta de Hierro de Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares, Madrid (P.G.-P.) - both in Spain; Chaim Sheba Medical Center, Ramat Gan and Tel Aviv University, Tel Aviv, Israel (M.A.); Hospital Companhia União Fabril Descobertas, Lisbon, Portugal (N.C.); Northwestern University Feinberg School of Medicine, Chicago (L.C.); the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (C.J.C., M.M.Y.L.), and Radcliffe Department of Medicine, University of Oxford, Oxford (H.W.) - both in the United Kingdom; Charité Campus Virchow-Klinikum, Berlin (H.-D.D.); Département de Cardiologie, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris (A.A.H.); Beijing Anzhen Hospital, Capital Medical University, Beijing (C.-S.M.); the Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam (M.M.) and Zwolle (M.S.) - both in the Netherlands; Meyer Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Florence, Italy (I.O.); National Institute of Cardiology, Warsaw, Poland (A.O.); University of Pennsylvania Perelman School of Medicine, Philadelphia (A.T.O.); the Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, and the Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen (J.T.-H.); the Department of Cardiology, Motol University Hospital, Prague, Czech Republic (J.V.); Cytokinetics, South San Francisco (D.L.J., S.B.H., S.K., F.I.M., L.M., A.W.), and the University of California, San Francisco, San Francisco (T.P.A.) - both in California.
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J Am Soc Echocardiogr
June 2024
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Electronic address:
Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, exhibits left ventricular hypertrophy not secondary to other causes, with varied phenotypic expression. Enhanced actin-myosin interaction underlies excessive myocardial contraction, frequently resulting in dynamic obstruction within the left ventricle. Left ventricular outflow tract obstruction, occurring at rest or with provocation in 75% of HCM patients, portends adverse prognosis, contributes to symptoms, and is frequently a therapeutic target.
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