Doc2 is not associated with known regulated exocytotic or endosomal compartments in adrenal chromaffin cells

Doc2 is a CZ-domain-containing protein that is highly expressed in the nerv ous system and has a constitutively expressed isoform. It has been implicat ed as a potential Ca2+ sensor in regulated exocytosis, and has been suggest ed to be associated with synaptic vesicles. To examine whether Doc2 is asso ciated with synaptic-like microvesicles (SLMVs) or dense-core granules in n euroendocrine cells, we examined the distribution of Doc? in subcellular fr actionation of chromaffin cells of the adrenal medulla and in PC12 cells. D oc2 did not co-distribute with SLMVs from either cell type. but did appear to co-distribute with dense-core granules from PC12 cells. In contrast, it was not associated with the dense-core granules during subcellular fraction ation of the adrenal medulla, and nor did it appear to be associated with e ndosomes, cis-Golgi or the trans-Golgi network. In contrast, Doc2 co-distri buted under all conditions with a mitochondrial marker. We conclude that Do c2 is not a general component of regulated secretory vesicles, but may inst ead be associated with mitochondria.