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GGA function is required for maturation of neuroendocrine secretory granules. 2006

Or Kakhlon, and Prabhat Sakya, and Banafshe Larijani, and Rose Watson, and Sharon A Tooze
Secretory Pathway Laboratories, Cancer Research UK, London Research Institute, London, UK.

Secretory granule (SG) maturation has been proposed to involve formation of clathrin-coated vesicles (CCVs) from immature SGs (ISGs). We tested the effect of inhibiting CCV budding by using the clathrin adaptor GGA (Golgi-associated, gamma-ear-containing, ADP-ribosylation factor-binding protein) on SG maturation in neuroendocrine cells. Overexpression of a truncated, GFP-tagged GGA, VHS (Vps27, Hrs, Stam)-GAT (GGA and target of myb (TOM))-GFP led to retention of MPR, VAMP4, and syntaxin 6 in mature SGs (MSGs), suggesting that CCV budding from ISGs is inhibited by the SG-localizing VHS-GAT-GFP. Furthermore, VHS-GAT-GFP-overexpression disrupts prohormone convertase 2 (PC2) autocatalytic cleavage, processing of secretogranin II to its product p18, and the correlation between PC2 and p18 levels. All these effects were not observed if full-length GGA1-GFP was overexpressed. Neither GGA1-GFP nor VHS-GAT-GFP perturbed SG protein budding from the TGN, or homotypic fusion of ISGs. Reducing GGA3 levels by using short interfering (si)RNA also led to VAMP4 retention in SGs, and inhibition of PC2 activity. Our results suggest that inhibition of CCV budding from ISGs downregulates the sorting from the ISGs and perturbs the intragranular activity of PC2.

UI MeSH Term Description Entries
D008561 Membrane Fusion The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. Fusion, Membrane,Fusions, Membrane,Membrane Fusions
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002864 Chromogranins A group of acidic proteins that are major components of SECRETORY GRANULES in the endocrine and neuroendocrine cells. They play important roles in the aggregation, packaging, sorting, and processing of secretory protein prior to secretion. They are cleaved to release biologically active peptides. There are various types of granins, usually classified by their sources. Chromogranin,Granin,Secretogranin,Secretogranins,Granins
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D016716 PC12 Cells A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation. Pheochromocytoma Cell Line,Cell Line, Pheochromocytoma,Cell Lines, Pheochromocytoma,PC12 Cell,Pheochromocytoma Cell Lines
D017527 Receptor, IGF Type 2 A receptor that is specific for IGF-II and mannose-6-phosphate. The receptor is a 250-kDa single chain polypeptide which is unrelated in structure to the type 1 IGF receptor (RECEPTOR, IGF TYPE 1) and does not have a tyrosine kinase domain. IGF Type 2 Receptor,IGF-II Receptor,Receptor, IGF-II,Receptor, Insulin-Like Growth Factor II,Receptor, Insulin-Like Growth Factor Type 2,Receptor, Mannose-6-Phosphate,IGF-2 Receptor,Insulin-Like-Growth-Factor II Receptor,Mannose-6-Phosphate Receptor,Receptors, IGF-2,Receptors, Insulin-Like Growth Factor II,IGF 2 Receptor,IGF II Receptor,IGF-2 Receptors,Insulin Like Growth Factor II Receptor,Mannose 6 Phosphate Receptor,Receptor, IGF II,Receptor, IGF-2,Receptor, Insulin Like Growth Factor II,Receptor, Insulin Like Growth Factor Type 2,Receptor, Insulin-Like-Growth-Factor II,Receptor, Mannose 6 Phosphate,Receptors, IGF 2,Receptors, Insulin Like Growth Factor II
D045706 Proprotein Convertase 2 A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN. Prohormone Convertase, PC2,Endopeptidase PC2,Neuroendocrine Convertase PC2,PC2 Endoprotease,PC2 Prohormone Convertase,PC2 Protein,Prohormone Convertase 2,Prohormone Convertase PC2,Proinsulin Convertase 2,Convertase 2, Prohormone,Convertase 2, Proinsulin,Convertase PC2, Neuroendocrine,Convertase PC2, Prohormone,Convertase, PC2 Prohormone,Endoprotease, PC2,PC2, Endopeptidase
D049452 Green Fluorescent Proteins Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH. Green Fluorescent Protein,Green-Fluorescent Protein,Green-Fluorescent Proteins,Fluorescent Protein, Green,Fluorescent Proteins, Green,Protein, Green Fluorescent,Protein, Green-Fluorescent,Proteins, Green Fluorescent,Proteins, Green-Fluorescent
D050765 Qa-SNARE Proteins A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES. Qa-SNAREs,Syntaxin,Syntaxin 10,Syntaxin 10 Protein,Syntaxin 11,Syntaxin 11 Protein,Syntaxin 13,Syntaxin 13 Protein,Syntaxin 17,Syntaxin 17 Protein,Syntaxin 18,Syntaxin 18 Protein,Syntaxin 1A Homologs,Syntaxin 3,Syntaxin 3 Protein,Syntaxin 3A,Syntaxin 3A Protein,Syntaxin 3B,Syntaxin 3B Protein,Syntaxin 3C,Syntaxin 3C Protein,Syntaxin 3D,Syntaxin 3D Protein,Syntaxin 4,Syntaxin 4 Protein,Syntaxin 5,Syntaxin 5 Protein,Syntaxin 6,Syntaxin 6 Protein,Syntaxin 7,Syntaxin 7 Protein,Syntaxin 8,Syntaxin 8 Protein,Syntaxin Protein,Syntaxin Proteins,Syntaxins,Protein, Syntaxin,Protein, Syntaxin 11,Proteins, Syntaxin,Qa SNARE Proteins,Qa SNAREs

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