CAPS (MAMMALIAN UNC-31) PROTEIN LOCALIZES TO MEMBRANES INVOLVED IN DENSE-CORE VESICLE EXOCYTOSIS

CAPS is a neural/endocrine-specific protein discovered as a cytosolic factor required for Ca2+-activated dense-core vesicle (DCV) exocytosis in permeable neuroendocrine cells. We report that CAPS is also a memb rane-associated, peripherally bound protein in brain homogenates that localizes selectively to plasma membranes and to DCVs but not to small clear synaptic vesicles (SVs). CAPS exhibits high affinity and satura ble binding to DCVs by interaction with bilayer phospholipids. Specifi c CAPS antibodies inhibit Ca2+-activated norepinephrine release from l ysed synaptosomes that contain membrane-associated CAPS, indicating th at membrane-bound CAPS is essential for neural DCV exocytosis. CAPS is a functional component of the exocytotic machinery that localizes sel ectively to DCVs, and it may confer distinct regulatory features on ne uropeptide and biogenic amine transmitter secretion.