Sorting of a Constitutive Secretory Protein to the Regulated Secretory Pathway of Exocrine Cells

1999 ◽  
Vol 257 (2) ◽  
pp. 545-548 ◽  
Author(s):  
Sven-Ulrik Gorr ◽  
Yancy R. Moore
Keyword(s):  
Secretory Pathway ◽  
Secretory Protein ◽  
Exocrine Cells ◽  
Regulated Secretory Pathway

Prohormone transport through the secretory pathway of neuroendocrine cells

2000 ◽  
Vol 78 (3) ◽  
pp. 289-298 ◽  
Author(s):  
Roland P Kuiper ◽  
Gerard JM Martens
Keyword(s):  
Secretory Pathway ◽  
Potential Role ◽  
Protein Transport ◽  
Secretory Granules ◽  
Secretory Protein ◽  
Neuroendocrine Cells ◽  
Secretory Proteins ◽  
Regulated Secretory Pathway ◽  
Made In

En route through the secretory pathway of neuroendocrine cells, prohormones pass a series of membrane-bounded compartments. During this transport, the prohormones are sorted to secretory granules and proteolytically cleaved to bioactive peptides. Recently, progress has been made in a number of aspects concerning secretory protein transport and sorting, particularly with respect to transport events in the early regions of the secretory pathway. In this review we will deal with some of these aspects, including: i) selective exit from the endoplasmic reticulum via COPII-coated vesicles and the potential role of p24 putative cargo receptors in this process, ii) cisternal maturation as an alternative model for protein transport through the Golgi complex, and iii) the mechanisms that may be involved in the sorting of regulated secretory proteins to secretory granules. Although much remains to be learned, interesting new insights into the functioning of the secretory pathway have been obtained.Key words: regulated secretory pathway, p24 family, vesicular transport, POMC, protein sorting, secretory granule, Xenopus laevis.

scholarly journals Reconstitution in vitro of the pH-dependent aggregation of pancreatic zymogens en route to the secretory granule: implication of GP-2

1993 ◽  
Vol 291 (1) ◽  
pp. 289-296 ◽  
Author(s):  
F A Leblond ◽  
G Viau ◽  
J Lainé ◽  
D Lebel
Keyword(s):  
Secretory Granule ◽  
Secretory Pathway ◽  
Relative Proportion ◽  
Secretory Protein ◽  
Secretory Proteins ◽  
Zymogen Granule ◽  
Granule Membrane ◽  
Regulated Secretory Pathway ◽  
Golgi Network

Regulated secretory proteins are thought to be sorted in the trans-Golgi network (TGN) via selective aggregation. To elucidate the biogenesis of the secretory granule in the exocrine pancreas, we reconstituted in vitro the conditions of pH and ions believed to exist in the TGN using the end product of this sorting process, the zymogen granule contents. Protein aggregation was dependent on pH (acidic) and on the presence of cations (10 mM Ca2+, 150 mM K+) to reproduce the pattern of proteins found in the granule. The constitutive secretory protein IgG was excluded from these aggregates. Zymogen aggregation correlated with the relative proportion of the major granule membrane protein GP-2 in the assay. These results show that the glycosylphosphatidylinositol-anchored protein GP-2 co-aggregates with zymogens in the acidic environment believed to exist in the pancreatic TGN, and thus suggest that GP-2 would function as a membrane anchor for zymogen aggregates, facilitating their entrapment in budding vesicles directed towards the regulated secretory pathway.

scholarly journals Sorting of the Neuroendocrine Secretory Protein Secretogranin II into the Regulated Secretory Pathway

2008 ◽  
Vol 283 (17) ◽  
pp. 11807-11822 ◽  
Author(s):  
Maïté Courel ◽  
Michael S. Vasquez ◽  
Vivian Y. Hook ◽  
Sushil K. Mahata ◽  
Laurent Taupenot
Keyword(s):  
Secretory Pathway ◽  
Secretory Protein ◽  
Secretogranin Ii ◽  
Regulated Secretory Pathway

scholarly journals Salivary glands as a potential gene transfer target for gene therapeutics of some monogenetic endocrine disorders

2005 ◽  
Vol 185 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Antonis Voutetakis ◽  
Ioannis Bossis ◽  
Marc R Kok ◽  
Weitian Zhang ◽  
Jianghua Wang ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Salivary Glands ◽  
Viral Vectors ◽  
Secretory Pathway ◽  
Protein Localization ◽  
Secretory Protein ◽  
Stable Gene ◽  
Endocrine Disorders ◽  
Target Tissue ◽  
Regulated Secretory Pathway

Salivary glands (SGs) exhibit several important features which are also common to endocrine glands: self-containment due to a surrounding capsule, highly efficient protein production and the ability to secrete proteins into the bloodstream. We have hypothesized that SGs are potentially useful as gene transfer targets for the correction of inherited monogenetic endocrine disorders. In the present communication, we extend our studies and attempt to test our hypothesis by comparing the efficacy of two commonly used viral vectors and the resulting serum and salivary distribution of transgene encoded hormones. A low dose (5 ×109 particles) of either an adenoviral serotype 5 (Ad5) vector encoding the human erythropoietin (hEPO) cDNA or an adeno-associated virus sero-type 2 (AAV2) vector encoding either the hEPO or human growth hormone (hGH) cDNA was administered to individual submandibular SGs of Balb/c mice. Serum and salivary hEPO and hGH levels were determined at defined time points. Two additional recombinant viruses encoding enhanced green fluorescence protein (GFP) were also used (AdGFP and AAVGFP) in order to perform immunohistochemical analyses of transgenic protein localization in SG sections post-administration. AAV2 vectors led to stable gene transfer unlike the results with the Ad5 vectors. Indeed, in one mouse we observed hEPO production for a period of two years after administration of AAVhEPO to SGs. hEPO, which is a constitutive pathway secretory protein, was readily secreted into the bloodstream from the SGs, yielding therapeutically adequate serum levels. Conversely, hGH, a regulated secretory pathway protein, was preferentially secreted into saliva. SGs may be an attractive candidate target tissue for gene therapeutics of some monogenetic endocrine deficiency disorders. At present, AAV2 vectors seem particularly useful for such applications, and transgenes encoding constitutive secretory pathway hormones are more suitable for this application with SGs than those encoding regulated secretory pathway hormones.

scholarly journals Constitutive and basal secretion from the endocrine cell line, AtT-20.

1991 ◽  
Vol 112 (5) ◽  
pp. 843-852 ◽  
Author(s):  
L Matsuuchi ◽  
R B Kelly
Keyword(s):  
Cell Line ◽  
Secretory Pathway ◽  
Secretory Granules ◽  
Secretory Protein ◽  
Dense Core ◽  
Wild Type ◽  
Dna Encoding ◽  
Basal Secretion ◽  
Constitutive Secretion ◽  
Regulated Secretory Pathway

A variant of the ACTH-secreting pituitary cell line, AtT-20, has been isolated that does not make ACTH, sulfated proteins characteristic of the regulated secretory pathway, or dense-core secretory granules but retains constitutive secretion. Unlike wild type AtT-20 cells, the variant cannot store or release on stimulation, free glycosaminoglycan (GAG) chains. In addition, the variant cells cannot store trypsinogen or proinsulin, proteins that are targeted to dense core secretory granules in wild type cells. The regulated pathway could not be restored by transfecting with DNA encoding trypsinogen, a soluble regulated secretory protein targeted to secretory granules. A comparison of secretion from variant and wild type cells allows a distinction to be made between constitutive secretion and basal secretion, the spontaneous release of regulated proteins that occurs in the absence of stimulation.

scholarly journals Somatostatin is targeted to the regulated secretory pathway of gonadotrophs in transgenic mice expressing a metallothionein-somatostatin gene.

1986 ◽  
Vol 261 (34) ◽  
pp. 16260-16263
Author(s):  
M J Low ◽  
P J Stork ◽  
R E Hammer ◽  
R L Brinster ◽  
M J Warhol ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Secretory Pathway ◽  
Regulated Secretory Pathway

scholarly journals amontillado, the Drosophila Homolog of the Prohormone Processing Protease PC2, Is Required During Embryogenesis and Early Larval Development

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 227-237 ◽  
Author(s):  
Lowell Y M Rayburn ◽  
Holly C Gooding ◽  
Semil P Choksi ◽  
Dhea Maloney ◽  
Ambrose R Kidd ◽  
...  
Keyword(s):  
Larval Development ◽  
Secretory Pathway ◽  
Larval Growth ◽  
Peptide Hormones ◽  
Complementation Group ◽  
Prohormone Processing ◽  
Complementation Groups ◽  
Regulated Secretory Pathway ◽  
Processing Protease ◽  
Larval Molt

Abstract Biosynthesis of most peptide hormones and neuropeptides requires proteolytic excision of the active peptide from inactive proprotein precursors, an activity carried out by subtilisin-like proprotein convertases (SPCs) in constitutive or regulated secretory pathways. The Drosophila amontillado (amon) gene encodes a homolog of the mammalian PC2 protein, an SPC that functions in the regulated secretory pathway in neuroendocrine tissues. We have identified amon mutants by isolating ethylmethanesulfonate (EMS)-induced lethal and visible mutations that define two complementation groups in the amon interval at 97D1 of the third chromosome. DNA sequencing identified the amon complementation group and the DNA sequence change for each of the nine amon alleles isolated. amon mutants display partial embryonic lethality, are defective in larval growth, and arrest during the first to second instar larval molt. Mutant larvae can be rescued by heat-shock-induced expression of the amon protein. Rescued larvae arrest at the subsequent larval molt, suggesting that amon is also required for the second to third instar larval molt. Our data indicate that the amon proprotein convertase is required during embryogenesis and larval development in Drosophila and support the hypothesis that AMON acts to proteolytically process peptide hormones that regulate hatching, larval growth, and larval ecdysis.

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