Analysis of calcium signaling in C. elegans The goal of this project is to analyze mechanisms controlling signaling by voltage-activated calcium (CaV) channels. In neurons and muscles, brief cytoplasmic calcium transients efficiently and rapidly activate downstream effectors, often on millisecond time scales. One general mechanism that promotes signal speed and efficiency is tight spatial coupling between CaV channels and their effectors, which is termed calcium nanodomain signaling. We propose three Aims to study nanodomain signaling by CaV channels. First, we identify genes required to promote coupling of CaV1 (L-type) channels to two effectors, calcium activated BK potassium channels and ryanodine receptors (RYR), which are calcium release channels in the endoplasmic reticulum. Second, we test models for how the threshold is set for activity induced gene transcription, and if this threshold is shifted by mutations in specific calcium activated signaling components or by endogenous neuropeptides. Third, we ask how CaV1 and 2 channels are localized at presynaptic terminals, which dictates neurotransmitter release probability. These Aims address fundamental mechanisms controlling neuron and muscle physiology.