The β-cell primary cilium is an autonomous Ca(2+) compartment for paracrine GABA signaling

The primary cilium is an organelle present in most adult mammalian cells that is considered as an antenna for sensing the local microenvironment. Here, we use intact mouse pancreatic islets of Langerhans to investigate signaling properties of the primary cilium in insulin-secreting β-cells. We find that GABA(B1) receptors are strongly enriched at the base of the cilium, but are mobilized to more distal locations upon agonist binding. Using cilia-targeted Ca(2+) indicators, we find that activation of GABA(B1) receptors induces selective Ca(2+) influx into primary cilia through a mechanism that requires voltage-dependent Ca(2+) channel activation. Islet β-cells utilize cytosolic Ca(2+) increases as the main trigger for insulin secretion, yet we find that increases in cytosolic Ca(2+) fail to propagate into the cilium, and that this isolation is largely due to enhanced Ca(2+) extrusion in the cilium. Our work reveals local GABA action on primary cilia that involves Ca(2+) influx and depends on restricted Ca(2+) diffusion between the cilium and cytosol.