MOLECULAR DIVERSITY IN NEUROSECRETION - REFLECTIONS ON THE HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM

1. The diversity of molecules involved in various aspects of neurosecr etion, such as proprotein processing, axonal transport of large dense core vesicles (LDCVs), and regulated secretion, is discussed in the co ntext of the hypothalamo-neurohypophysial system (HNS). 2. Recent stud ies have uncovered a family of at least seven processing enzymes known as proprotein convertases (PCs) which are involved in proteolytically cleaving protein precursors at paired basic amino acid motifs to yiel d biologically active peptides. Three of these, PC1(3), 2, and 5, are found in neurons and are involved in producing regulated secretory pep tide products. 3. The axonal transport of LDCVs occurs on microtubule tracks by still unknown mechanisms. There are over 11 distinct kinesin -related molecules that have now been identified as possible microtubu le motor candidates. 4. Calcium channels in the nervous system are kno wn to be derived from at least five alpha-subunit and four beta-subuni t genes with multiple alternatively spliced isoforms in each case. The se could account, in part, for the varied calcium currents found in th e HNS. 5. The large number of proteins and isoforms now demonstrated t o be involved in regulated secretion are discussed, with a focus on LD CV compositions and the synaptotagmin gene family.