Secretory granule biogenesis and neuropeptide sorting to the regulated secretory pathway in neuroendocrine cells

  title={Secretory granule biogenesis and neuropeptide sorting to the regulated secretory pathway in neuroendocrine cells},
  author={Y. Peng Loh and Taeyoon Kim and Yazmin M. Rodriguez and Niamh X. Cawley},
  journal={Journal of Molecular Neuroscience},
Neuropeptide precursors synthesized at the rough endoplasmic reticulum are transported and sorted at the trans-Golgi network (TGN) to the granules of the regulated secretory pathway (RSP) of neuroendocrine cells. They are then processed into active peptides and stored in large dense-core granules (LDCGs) until secreted upon stimulation. We have studied the regulation of biogenesis of the LDCGs and the mechanism by which neuropeptide precursors, such as pro-opiomelanocortin (POMC), are sorted… 

Protease nexin-1 promotes secretory granule biogenesis by preventing granule protein degradation.

CgA increases DCG biogenesis in endocrine cells by up-regulating PN-1 expression to stabilize granule proteins against degradation, which is a novel mechanism for the regulation of CgA-mediated DCGBiogenesis.

3 Neurosecretory Protein Trafficking and Dense-Core Granule Biogenesis in Neuroendocrine Cells

Studies haveidentified chromogranin A (CgA) as a regulator of quantitative DCG biogenesis in neuroendocrine cells by regulating the stability of secretorygranule proteins in the Golgi apparatus, thereby controlling the number of DCGs that can be formed.

Role of H+-ATPase-mediated Acidification in Sorting and Release of the Regulated Secretory Protein Chromogranin A

It is proposed that a V-ATPase-mediated pH gradient in the secretory pathway is an important factor for the formation of dense-core granules by regulating the ability of CgA to form aggregates, a crucial step that may underlie the granulogenic function of the protein.

Carboxypeptidase E, an essential element of the regulated secretory pathway, is expressed and partially co-localized with chromogranin A in chicken thymus

The findings suggest that the diffuse neuroendocrine system serves as a relay for nervous stimuli delivered by the sympathetic and/or parasympathetic nervous system, potentially enabling thymopoiesis to be fine-tuned via the regulated secretory pathway by a variety of physical and environmental factors.

ACTH: cellular peptide hormone synthesis and secretory pathways.

Adrenocorticotrophic hormone (ACTH) is derived from the prohormone, pro-opiomelanocortin (POMC), which is itself released from cells and found in the human circulation at concentrations greater than ACTH.

Secretogranin III Directs Secretory Vesicle Biogenesis in Mast Cells in a Manner Dependent upon Interaction with Chromogranin A1

The results show that over-expression of SgIII in mast cells is sufficient to cause an expansion of a granular compartment in these cells, and novel granules store inflammatory mediators that are released in response to physiological stimuli, indicating that they function as bona fide secretory vesicles.

Expression of pro-Muclin in pancreatic AR42J cells induces functional regulated secretory granules.

The data show that pro-Muclin acts as a sorting receptor that can induce RSG, and that its cytosolic tail is important in this process.

A large form of secretogranin III functions as a sorting receptor for chromogranin A aggregates in PC12 cells.

It is suggested that the sorting function of secretogranin III for chromogran in A is common in PC12 and chromaffin cells as well as in other endocrine cells, and a small amount of secretoglutin III is able to sort chromogsranin A aggregates together with adrenomedullin to secretory granules.

Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles

It is found that LDCVs were associated with multiple receptors, channels and signaling molecules, suggesting that neuronal sensitivity is modulated by an LDCV-mediated mechanism, enabling a rapid, activity-dependent modulation of neuronal sensitivity.

The granin VGF promotes genesis of secretory vesicles, and regulates circulating catecholamine levels and blood pressure

A role for VGF in adrenal LDCV formation and the regulation of catecholamine levels and blood pressure is established and acute and chronic administration of the VGF‐derived peptide TLQP‐21 to rodents decreased blood pressure.



Mechanism of Sorting Proopiomelanocortin and Proenkephalin to the Regulated Secretory Pathway of Neuroendocrine Cells

POMC and PE are sorted to the RSP at the TGN by a mechanism involving the interaction of a specific sorting signal on these molecules with the sorting receptor, CPE.

Mannose 6–Phosphate Receptors Are Sorted from Immature Secretory Granules via Adaptor Protein AP-1, Clathrin, and Syntaxin 6–positive Vesicles

It is hypothesized that during secretory granule maturation, MPR–ligand complexes and syntaxin 6 are removed from IGs by AP-1/clathrin-coated vesicles, and then delivered to endosomes, just as was previously observed in β cells.

Carboxypeptidase E, a prohormone sorting receptor, is anchored to secretory granules via a C-terminal transmembrane insertion.

It is concluded that the membrane-binding domain of CPE must adopt an alpha-helical configuration to bind to lipids, and that CPE may require another integral membrane "chaperone" protein to insert through the lipid bilayer in a transmembrane fashion.

Lipid Raft Association of Carboxypeptidase E Is Necessary for Its Function as a Regulated Secretory Pathway Sorting Receptor*

It is proposed that the sorting receptor function of CPE necessitates its interaction with glycosphingolipid-cholesterol rafts at the TGN, thereby anchoring it in position to bind to its prohormone cargo.

Disruption of a receptor-mediated mechanism for intracellular sorting of proinsulin in familial hyperproinsulinemia.

Using a combination of molecular modeling and site-directed mutagenesis, structural molecular motifs in proinsulin are identified that are necessary for correct sorting into secretory granules of endocrine cells and membrane carboxypeptidase E (CPE), previously identified as a prohormone-sorting receptor, is essential forProinsulin sorting.

Identification of a novel prohormone sorting signal-binding site on carboxypeptidase E, a regulated secretory pathway-sorting receptor.

Results indicate that the sorting signal of POMC, proinsulin, and proenkephalin specifically interacts with Arg255 and Lys260 at a novel binding site, independent of the active site on CPE.

Effects of sex steroids on secretory granule formation in gonadotropes of castrated male rats with respect to granin expression.

In castrated rats supplied with an estradiol implant, the expression and content of CgA in the pituitary were remarkably suppressed, and large secretory granules disappeared from gonadotropes, suggesting that the expression of C gA in gonADotropes is regulated differently by male and female sex steroids.