Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin

Abstract

Synaptotagmin is an abundant synaptic vesicle-associated protein proposed to be involved in calcium-mediated neurotransmitter release. Our molecular and genetic results demonstrate that, although synaptotagmin is required for the proper function of the presynaptic nerve terminal in C. elegans, some neurotransmitter release persists in synaptogamin mutants. In C. elegans neurons, synaptotagmin is localized to regions known to be rich in synapses and appears to be associated with synaptic vesicles. Mutants defective in the synaptotagmin gene, called snt-1, exhibit severe behavioral abnormalities that are characteristic of deficiencies in synaptic function, including severe locomotion, feeding, and defecation defects. The mutants are defective in exocytosis, since they accumulate acetylcholine, and are resistant to cholinesterase inhibitors, but they nevertheless remain sensitive to cholinergic receptor agonists. In spite of these exocytic defects, snt-1 mutants are capable of coordinated motor movements, indicating that the mutants do not have a complete block of neurotransmitter release.

Electrical activity and behavior in the pharynx of caenorhabditis elegans

“…They appear smaller and more numerous. These data support the conclusion drawn from the behavioral phenotypes of snt-1, that synaptic function persists but is abnormal in the absence of synaptotagmin (Nonet et al, 1993).…”

“…For example, we can test whether genes with a proposed role in neurotransmission are necessary for the P phase transients. One such gene, snt-I, encodes the C. elegans homolog of vertebrate synaptotagmin (Nonet et al, 1993). Synaptotagmin is a protein found in synaptic vesicles and is thought to play a key role in the regulated release of neurotransmitter (Bommert et al, 1993;DiAntonio et al, 1993;Elferink et al, 1993;Nonet et al, 1993).…”

“…Synaptotagmin is a protein found in synaptic vesicles and is thought to play a key role in the regulated release of neurotransmitter (Bommert et al, 1993;DiAntonio et al, 1993;Elferink et al, 1993;Nonet et al, 1993). However, the behavioral phenotypes of C. elegans mutants with a complete loss of snt-I function suggest that some regulated synaptic function persists in the absence of synaptotagmin (Nonet et al, 1993). To see whether synaptic transmission does indeed persist, we recorded from a snt-I null mutant.…”

“…Furthermore, P phase transients in the EPG of worms mutant for the synaptotagmin gene snt-1 appear abnormal. Since synaptotagmin is expressed in neurons at synapses (Nonet et al, 1993) and affects synaptic transmission (for review see Popov and Poo, 1993), this result suggests that the P phase transients are synaptic in origin.…”

Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non‐cell‐autonomous stress response

“…We first focused on the calcium sensor synaptotagmin (SNT‐1), required for Ca 2+ ‐induced vesicle exocytosis (Brose et al ., 1992), and synaptojanin (UNC‐26), required for vesicle recycling (Harris et al ., 2000). Mutations in these genes decrease synaptic transmission (Nonet et al ., 1993; Harris et al ., 2000). In contrast, diacylglycerol kinase‐1 (DGK‐1) represses synaptic exocytosis, and therefore, mutations in dgk‐1 enhance synaptic transmission (Nurrish et al ., 1999).…”