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

@article{Loh2007SecretoryGB,
  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},
  year={2007},
  volume={22},
  pages={63-71}
}
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… Expand
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It is concluded that secretory granules undergo a switch from unregulated to regulated secretory carriers during biogenesis, and the existence of such a switch may provide a mechanism for cells to modulate their secretory activities under different physiological conditions. Expand
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Results show that in a cell-free system, a constitutive and a regulated secretory protein are sorted upon exit from the trans-Golgi network. Expand
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TLDR
The role of CPE as a sorting receptor for other RSP proteins that contain sorting signals (proinsulin, proenkephalin, and chromogranin A) was investigated in neuroendocrine cells (Neuro-2a) stably expressing CPE antisense RNA, suggesting the existence of other sorting receptors for the RSP. Expand
Mechanism of Sorting Proopiomelanocortin and Proenkephalin to the Regulated Secretory Pathway of Neuroendocrine Cells
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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. Expand
Mannose 6–Phosphate Receptors Are Sorted from Immature Secretory Granules via Adaptor Protein AP-1, Clathrin, and Syntaxin 6–positive Vesicles
TLDR
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. Expand
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TLDR
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Lipid Raft Association of Carboxypeptidase E Is Necessary for Its Function as a Regulated Secretory Pathway Sorting Receptor*
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TLDR
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. Expand
Identification of a novel prohormone sorting signal-binding site on carboxypeptidase E, a regulated secretory pathway-sorting receptor.
TLDR
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. Expand
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