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- W4224939653 abstract "Requirements for vesicle fusion within the heart remain poorly understood, despite the multitude of processes that necessitate proper intracellular trafficking within cardiomyocytes. Here, we show that Syntaxin 4 (STX4), a target-Soluble N-ethylmaleimide sensitive factor attachment receptor (t-SNARE) protein, is required for normal vertebrate cardiac conduction and vesicular transport. Two patients were identified with damaging variants in STX4. A patient with a homozygous R240W missense variant displayed biventricular dilated cardiomyopathy, ectopy, and runs of non-sustained ventricular tachycardia, sensorineural hearing loss, global developmental delay, and hypotonia, while a second patient displayed severe pleiotropic abnormalities and perinatal lethality. CRISPR/Cas9-generated stx4 mutant zebrafish exhibited defects reminiscent of these patients' clinical presentations, including linearized hearts, bradycardia, otic vesicle dysgenesis, neuronal atrophy, and touch insensitivity by 3 days post fertilization. Imaging of Vamp2+ vesicles within stx4 mutant zebrafish hearts showed reduced docking to the cardiomyocyte sarcolemma. Optical mapping of the embryonic hearts coupled with pharmacological modulation of Ca2+ handling together support that zebrafish stx4 mutants have a reduction in L-type Ca2+ channel modulation. Transgenic overexpression of zebrafish Stx4R241W, analogous to the first patient's STX4R240W variant, indicated that the variant is hypomorphic. Thus, these data show an in vivo requirement for SNAREs in regulating normal embryonic cardiac function and that variants in STX4 are associated with pleiotropic human disease, including cardiomyopathy." @default.
- W4224939653 created "2022-04-28" @default.
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- W4224939653 creator A5067076195 @default.
- W4224939653 creator A5083881992 @default.
- W4224939653 creator A5091779911 @default.
- W4224939653 date "2022-07-01" @default.
- W4224939653 modified "2023-09-25" @default.
- W4224939653 title "Stx4 is required to regulate cardiomyocyte Ca2+ handling during vertebrate cardiac development" @default.
- W4224939653 cites W1561955874 @default.
- W4224939653 cites W1728657678 @default.
- W4224939653 cites W1808711893 @default.
- W4224939653 cites W190578437 @default.
- W4224939653 cites W1938070107 @default.
- W4224939653 cites W1969604092 @default.
- W4224939653 cites W1969744517 @default.
- W4224939653 cites W1970106304 @default.
- W4224939653 cites W1970413157 @default.
- W4224939653 cites W1971386182 @default.
- W4224939653 cites W1973449157 @default.
- W4224939653 cites W1978155997 @default.
- W4224939653 cites W1984338606 @default.
- W4224939653 cites W1984698971 @default.
- W4224939653 cites W1995406808 @default.
- W4224939653 cites W2005553942 @default.
- W4224939653 cites W2024136850 @default.
- W4224939653 cites W2024405748 @default.
- W4224939653 cites W2027686135 @default.
- W4224939653 cites W2032868089 @default.
- W4224939653 cites W2034691490 @default.
- W4224939653 cites W2036467191 @default.
- W4224939653 cites W2041877406 @default.
- W4224939653 cites W2051681596 @default.
- W4224939653 cites W2051978340 @default.
- W4224939653 cites W2055202626 @default.
- W4224939653 cites W2058981056 @default.
- W4224939653 cites W2059145105 @default.
- W4224939653 cites W2063184625 @default.
- W4224939653 cites W2066402939 @default.
- W4224939653 cites W2067354100 @default.
- W4224939653 cites W2069272325 @default.
- W4224939653 cites W2073032316 @default.
- W4224939653 cites W2073187339 @default.
- W4224939653 cites W2077179726 @default.
- W4224939653 cites W2081558031 @default.
- W4224939653 cites W2086185798 @default.
- W4224939653 cites W2089238497 @default.
- W4224939653 cites W2089686748 @default.
- W4224939653 cites W2097294303 @default.
- W4224939653 cites W2098957812 @default.
- W4224939653 cites W2101816987 @default.
- W4224939653 cites W2103349369 @default.
- W4224939653 cites W2103441770 @default.
- W4224939653 cites W2107277218 @default.
- W4224939653 cites W2109686700 @default.
- W4224939653 cites W2112042956 @default.
- W4224939653 cites W2112528263 @default.
- W4224939653 cites W2112596275 @default.
- W4224939653 cites W2114460071 @default.
- W4224939653 cites W2115923216 @default.
- W4224939653 cites W2134268326 @default.
- W4224939653 cites W2135570564 @default.
- W4224939653 cites W2139648742 @default.
- W4224939653 cites W2141279088 @default.
- W4224939653 cites W2145187337 @default.
- W4224939653 cites W2148105023 @default.
- W4224939653 cites W2148171419 @default.
- W4224939653 cites W2150158001 @default.
- W4224939653 cites W2151589569 @default.
- W4224939653 cites W2151866362 @default.
- W4224939653 cites W2157022905 @default.
- W4224939653 cites W2160734881 @default.
- W4224939653 cites W2161533644 @default.
- W4224939653 cites W2162017885 @default.
- W4224939653 cites W2164386538 @default.
- W4224939653 cites W2164695230 @default.
- W4224939653 cites W2166747217 @default.
- W4224939653 cites W2168287692 @default.
- W4224939653 cites W2192080449 @default.
- W4224939653 cites W2195303995 @default.
- W4224939653 cites W2270303516 @default.
- W4224939653 cites W2296614526 @default.
- W4224939653 cites W2325244585 @default.
- W4224939653 cites W2347060853 @default.
- W4224939653 cites W2526945327 @default.
- W4224939653 cites W2559986107 @default.
- W4224939653 cites W2590061497 @default.
- W4224939653 cites W2594403371 @default.