Molecular Diversity in Neurosecretion: Reflections on the Hypothalamo-Neurohypophysial System

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SUMMARYThe diversity of molecules involved in various aspects of neurosecretion, such asproprotein processing, axonal transport of large dense core vesicles (LDCVs), and regulated secretion, is discussed in the context of the hypothalamo-neurohypophysial system (HNS).Recent studies 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 yield biologically active peptides. Three of these, PC1(3), 2, and 5, are found in neurons and are involved in producing regulatedsecretory peptide products.The axonal transport of LDCVs occurs on microtubule tracks by still unknown mechanisms. There are over 11 distinct kinesin-related molecules that have now beenidentified as possible microtubule motor candidates.Calcium channels in the nervous system are known to be derived from at leastfive α-subunit and four β-subunit genes with multiple alternatively spliced isoforms in each case. These could account, in part, for the varied calcium currents found in the HNS.The large number of proteins and isoforms now demonstrated to be involved inregulated secretion are discussed, with a focus on LDCV compositions and the synaptotag-min gene family.

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