title: Protein trafficking to chromaffin granules and proteolytic processing within regulated secretory vesicles of neuroendocrine chromaffin cells.
abstract: Proteolytic processing within secretory vesicles is required for the production and secretion of biologically active peptide neurotransmitters and hormones, known collectively as neuropeptides. This chapter addresses several new aspects of proteolysis in secretory vesicles, chromaffin granules, with respect to sorting proneuropeptides or prohormones into such regulated secretory vesicles that use specific prohormone sorting signals. Concomitant with prohormone sorting, evidence for the role of chromogranin A in secretory granule biogenesis is presented. Secretory vesicle function involves endogenous serpin protease inhibitors for the regulation of proteolysis. The novel serpins endopin 1 and endopin 2 possess high homology to a(1)-antichymotrypsin, yet they possess distinct target protease specificities. The serpins PAI-1 and neuroserpin are also localized to chromaffin granules. In addition, regulation of secretory vesicle function involves cytochrome b561 that regulates reducing equivalents to maintain the intravesicular redox state. These studies demonstrate multiple components as regulatory factors in the control of secretory vesicle function for the biosynthesis and secretion of neuropeptides and catecholamines.
authors.affiliation: Buck Institute for Age Research, Novato, California 94945, USA. vhook@buckinstitute.org
authors.forename: Vivian
authors.initials: V
authors.lastname: Hook
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
mesh_terms: D000818:Animals; D019439:Chromaffin Cells / Q000378:metabolism* / Q000502:physiology*; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism; D003573:Cytochrome b Group / Q000502:physiology; D016716:PC12 Cells; D021381:Protein Transport; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D053379:Chromogranin A; D002864:Chromogranins; D003573:Cytochrome b Group; C023646:cytochrome b561