Abstract
Processes underlying the formation of dense core secretory granules (DCGs) of neuroendocrine cells are poorly understood. Here, we present evidence that DCG biogenesis is dependent on the secretory protein secretogranin (Sg) II, a member of the granin family of pro-hormone cargo of DCGs in neuroendocrine cells. Depletion of SgII expression in PC12 cells leads to a decrease in both the number and size of DCGs and impairs DCG trafficking of other regulated hormones. Expression of SgII fusion proteins in a secretory-deficient PC12 variant rescues a regulated secretory pathway. SgII-containing dense core vesicles share morphological and physical properties with bona fide DCGs, are competent for regulated exocytosis, and maintain an acidic luminal pH through the V-type H(+)-translocating ATPase. The granulogenic activity of SgII requires a pH gradient along this secretory pathway. We conclude that SgII is a critical factor for the regulation of DCG biogenesis in neuroendocrine cells, mediating the formation of functional DCGs via its pH-dependent aggregation at the trans-Golgi network.
Highlights
Processes underlying the formation of dense core secretory granules (DCGs) of neuroendocrine cells are poorly understood
A granulogenic role for chromogranin A (CgA) and chromogranin B (CgB) is documented across cell lineages, where their expression induces the formation of granule-like structures competent for exocytosis (11, 12, 17–20)
SgII in the biogenesis of DCGs of sympathoadrenal chromaffin cells. This secretory protein has been extensively used as a marker of the regulated secretory pathway (53, 57, 58), its function in the formation of DCGs has not been carefully investigated, and so far it remains elusive (19, 22)
Summary
Processes underlying the formation of dense core secretory granules (DCGs) of neuroendocrine cells are poorly understood. SgII Induces the Formation of Reduction of SgII Expression Impairs Regulated Secretory Vesicular Structures in Neurosecretion-deficient A35C Cells—Peptide Trafficking into DCGs—The 36-amino acid peptide Consistent with the granulogenic activity of an SgII-Myc fusion neurotransmitter NPY is stored in DCGs of neuroendocrine protein in several non-neuroendocrine cell types (19), the trancells (25, 39 – 41).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
