Stimulation of Ca ²⁺ -dependent neurotransmitter release and presynaptic nerve terminal protein phosphorylation by calmodulin and a calmodulin-like protein isolated from synaptic vesicles

Abstract

Synaptic vesicles have a Ca2+-dependent protein kinase system that may play a role in mediating Ca2+-stimulated neurotransmitter release and vesicle function. Calcium's ability to initiate norepinephrine release and protein phosphorylation in synaptic vesicle preparations was shown to be stimulated by the presence of an endogenous heat-stable vesicle protein fraction. The heat stability and characteristics of this endogenous vesicle fraction were similar to those of calmodulin (Ca2+-dependent regular protein) isolated from rat and bovine brain. Calmodulin, like endogenous heat-stable vesicle factor, restored calcium's ability to stimulate vesicle neurotransmitter release and protein kinase activity. Calmodulin-like vesicle protein and purified calmodulin were also equally effective in stimulating cyclic nucleotide-dependent phosphodiesterase, further indicating that these two proteins are functionally equivalent. Depolarization-dependent Ca2+ uptake in intact synaptosomes simultaneously stimulated release of neurotransmitter and phosphorylation of particular synaptic vesicle proteins that were shown in the isolated vesicle preparation to be dependent on Ca2+ and calmodulin. The results suggest that calcium's effects on neurotransmitter release and presynaptic nerve terminal protein phosphorylation may be mediated by endogenous calmodulin-like proteins.

Boron and Calcium Sites Involved in Indole-3-Acetic Acid Transport in Sunflower Hypocotyl Segments

“…Several lines of investigation are being pursued by workers using animal cells (4). There is evidence for the possible involvement of the Ca-binding protein calmodulin in the phosphorylation of proteins involved in secretion (3). This could explain the specificity observed with the effectiveness of gM Ca in the cytoplasm in the presence of mm Mg.…”

Localization of calmodulin in rat cerebellum by immunoelectron microscopy

“…(11) have isolated postsynaptic densities and have shown that calmodulin represents a major protein component. A functional role for the calcium-binding protein is suggested by the studies of DeLorenzo and colleagues (9), who report that calmodulin stimulates dopamine release from isolated synaptosomes. Our studies reveal an intense reaction product in the postsynaptic region of cerebellar synapses and, thus, support these biochemical and functional observations.…”

3′,5′‐Cyclic Adenosine Monophosphate‐ and Ca2+‐Calmodulin‐Dependent Endogenous Protein Phosphorylation Activity in Membranes of the Bovine Chromaffin Secretory Vesicles: Identification of Two Phosphorylated Components as Tyrosine Hydroxylase and Protein Kinase Regulatory Subunit Type II

“…Protein phosphorylation systems have been postulated to participate in the events triggered b y secretory stimuli in t h e adrenal medulla (Amy and Kirshner, 1981), in nervous tissue (Krueger et al, 1977;DeLorenzo et al, 1979;Huttner and Greengard, 1979), and in other secretory systems, including mast cells (Sieghart et al, 1978) and blood platelets (Haslam and Lynham, 1977). In some of these studies the protein phosphorylation response as well as the secretory response were shown to be dependent on Ca2+ (Amy and Kirshner, 1981) or Ca2+ and calmodulin (DeLorenzo et al, 1979).…”