Dynamin 1 restrains vesicular release to a subquantal mode in mammalian adrenal chromaffin cells

Abstract

Dynamin 1 (dyn1) is required for clathrin-mediated endocytosis in most secretory (neuronal and neuroendocrine) cells. There are two modes of Ca 2+ -dependent catecholamine release from single dense-core vesicles: full-quantal (quantal) and subquantal in adrenal chromaffin cells, but their relative occurrences and impacts on total secretion remain unclear. To address this fundamental question in neurotransmission area using both sexes of animals, here we report the following: (1) dyn1-KO increased quantal size (QS, but not vesicle size/content) by ≥250% in dyn1-KO mice; (2) the KO-increased QS was rescued by dyn1 (but not its deficient mutant or dyn2); (3) the ratio of quantal versus subquantal events was increased by KO; (4) following a release event, more protein contents were retained in WT versus KO vesicles; and (5) the fusion pore size (d p ) was increased from ≤9to≥9 nm by KO. Therefore, Ca 2+ -induced exocytosis is generally a subquantal release in sympathetic adrenal chromaffin cells, implying that neurotransmitter release is generally regulated by dynamin in neuronal cells. Significance Statement Ca 2+ -dependent neurotransmitter release from a single vesicle is the primary event in all neurotransmission, including synaptic/ neuroendocrine forms. To determine whether Ca 2+ -dependent vesicular neurotransmitter release is “all-or-none” (quantal), we provide compelling evidence that most Ca 2+ -induced secretory events occur via the subquantal mode in native adrenal chromaffin cells. This subquantal release mode is promoted by dynamin 1, which is universally required for most secretory cells, including neurons and neuroendocrine cells. The present work with dyn1-KO mice further confirms that Ca 2+ -dependent transmitter release is mainly via subquantal mode, suggesting that subquantal release could be also important in other types of cells.