Munc13-1 Promotes Secretory Granule Exocytosis Through Two Separate Calcium-Dependent Mechanisms
نویسندگان
چکیده
Munc13 is central to priming of secretory granules for exocytosis, by allowing syntaxin engage into the SNARE complex. The protein enriched at release site in both (neuro)endocrine cells and neuronal synapses. contains a Ca2+-binding C2B domain, which may explain part Ca2+-dependence priming, but mechanism Ca2+ regulates are not understood. Here we used high-resolution TIRF microscopy patch-clamp electrophysiology understand how Ca2+-dependent recruitment Munc13-1 affects granule insulin secreting cells. We find strong correlation between probability amount present individual granules. By using single molecule observations, roughly 1:1:1 stoichiometry slowly diffusing fraction syntaxin-1 Munc18 moment exocytosis. absolute number (16.2 ±9.27 SD) suggest that limits Cis-SNARE complex formation. Elevated cytosolic or DAG promote recruiting plasma membrane, from it partitions sites. Overexpression likewise increased enhanced transient facilitation exocytosis did require translocation protein. A non-sensitive calcium mutant displayed activity without facilitation. In summary, vesicle two steps, its during activation site.
منابع مشابه
Secretory granule exocytosis.
Regulated exocytosis of secretory granules or dense-core granules has been examined in many well-characterized cell types including neurons, neuroendocrine, endocrine, exocrine, and hemopoietic cells and also in other less well-studied cell types. Secretory granule exocytosis occurs through mechanisms with many aspects in common with synaptic vesicle exocytosis and most likely uses the same bas...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2021
ISSN: ['0006-3495', '1542-0086']
DOI: https://doi.org/10.1016/j.bpj.2020.11.549