scholarly journals Promotion of intragranular co-aggregation with LH by enhancement of secretogranin II storage resulted in increased intracellular granule storage in gonadotrophs of GnRH-deprived male mice

Reproduction ◽  
2002 ◽  
pp. 267-277 ◽  
Author(s):  
JL Crawford ◽  
L Nicol ◽  
AS McNeilly ◽  
Keyword(s):  
Secretory Pathway ◽  
Immunogold Labelling ◽  
Male Mice ◽  
Secretogranin Ii ◽  
Mrna Content ◽  
Basal Plasma ◽  
Buserelin Treatment ◽  
B Mice ◽  
Regulated Secretory Pathway ◽  
And Control

Intracellular associations indicate that granins may play a role in the regulatory mechanisms involved in differential secretion of gonadotrophins. The effect of GnRH on mRNA expression, storage and secretory patterns of granins and gonadotrophins was investigated in male mice. GnRH antiserum (G/A) was injected into mice in the treatment group (n = 15) at 12 h intervals for 2 days and a subset (n = 9) was killed. Buserelin (G/A + B) was administered to the remaining mice (n = 6), which were killed 2 h later; control mice (n = 6) were killed at the onset of the study. LHb mRNA content was lower in G/A and G/A + B mice compared with controls, whereas plasma LH concentrations were higher in G/A + B mice. FSHbeta mRNA content did not change, whereas plasma FSH concentrations were lower in G/A mice compared with controls, and higher in G/A + B mice compared with both G/A and control mice. Secretogranin II (SgII) and CgA mRNA contents were not different between experimental groups. There were more granules per gonadotroph in G/A mice, and considerably fewer after Buserelin treatment. Immunogold labelling of gonadotrophs revealed the presence of LH(+ve)/SgII(+ve) and LH(+ve)/SgII(-ve) granules, and negligible numbers of LH(-ve)/SgII(+ve) granules. Both the numbers of LH(+ve)/SgII(+ve) granules and overall granule antigenicity for SgII were higher in G/A mice compared with controls and G/A + B mice. In contrast, there were fewer LH(+ve)/SgII(-ve) granules per gonadotroph in G/A mice compared with controls. In conclusion, absence of GnRH input to the pituitary gland resulted in preferential storage of SgII and subsequently increased intragranular co-aggregation with LH. Administration of Buserelin to G/A mice resulted in the apparent release of LH(+ve)/SgII(+ve) granules that was reflected by an increase in plasma LH concentrations, indicating that these granules were in the regulated secretory pathway. In contrast, secretion of LH(+ve)/SgII(-ve) granules did not appear to be influenced by the actions of Buserelin and, therefore, may have been destined for constitutive release, possibly to maintain basal plasma LH concentrations.

scholarly journals Transport via the regulated secretory pathway in semi-intact PC12 cells: role of intra-cisternal calcium and pH in the transport and sorting of secretogranin II.

1994 ◽  
Vol 127 (3) ◽  
pp. 693-705 ◽  
Author(s):  
L Carnell ◽  
H P Moore
Keyword(s):  
Pc12 Cells ◽  
Secretory Pathway ◽  
Secretory Granules ◽  
Ph Gradients ◽  
Secretogranin Ii ◽  
Prohormone Processing ◽  
Endoproteolytic Cleavage ◽  
Regulated Secretory Pathway ◽  
Gamma S

To gain insight into the mechanisms governing protein sorting, we have developed a system that reconstitutes both the formation of immature secretory granules and their fusion with the plasma membrane. Semi-intact PC12 cells were incubated with ATP and cytosol for 15 min to allow immature granules to form, and then in a buffer containing 30 microM [Ca2+]free to induce exocytosis. Transport via the regulated pathway, as assayed by the release of secretogranin II (SgII) labeled in the TGN, was inhibited by depletion of ATP, or by the inclusion of 100 microM GTP gamma S, 50 microM AlF3-5 or 5 micrograms/ml BFA. When added after immature granules had formed, GTP gamma S stimulated rather than inhibited exocytosis. Thus, exocytosis of immature granules in this system resembles the characteristics of fully matured granules. Transport of SgII via the regulated pathway occurred at a fourfold higher efficiency than glycosaminoglycan chains, indicating that SgII is sorted to some extent upon exit from the TGN. Addition of A23187 to release Ca2+ from the TGN had no significant effect on sorting of SgII into immature granules. In contrast, depletion of lumenal calcium inhibited the endoproteolytic cleavage of POMC and proinsulin. These results establish the importance of intra-cisternal Ca2+ in prohormone processing, but raise the question whether lumenal calcium is required for proper sorting of SgII into immature granules. Disruption of organelle pH gradients with an ionophore or a weak base resulted in the inhibition of transport via both the constitutive and the regulated pathways.

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 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.

scholarly journals Regulation of mdr2 P-glycoprotein expression by bile salts

1997 ◽  
Vol 321 (2) ◽  
pp. 389-395 ◽  
Author(s):  
Charles M. G. FRIJTERS ◽  
Roelof OTTENHOFF ◽  
Michel J. A. van WIJLAND ◽  
Carin M. J. van NIEUWKERK ◽  
Albert K. GROEN ◽  
...  
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Control Diet ◽  
Mrna Level ◽  
Northern Blotting ◽  
Mrna Levels ◽  
Male Mice ◽  
Complete Replacement ◽  
P Glycoprotein ◽  
Mrna Content

The phosphatidyl translocating activity of the mdr2 P-glycoprotein (Pgp) in the canalicular membrane of the mouse hepatocyte is a rate-controlling step in the biliary secretion of phospholipid. Since bile salts also regulate the secretion of biliary lipids, we investigated the influence of the type of bile salt in the circulation on mdr2 Pgp expression and activity. Male mice were fed a purified diet to which either 0.1% (w/w) cholate or 0.5% (w/w) ursodeoxycholate was added. This led to a near-complete replacement of the endogenous bile salt pool (mainly tauromuricholate) by taurocholate or tauroursodeoxycholate respectively. The phospholipid secretion capacity was then determined by infusion of increasing amounts of tauroursodeoxycholate. Cholate feeding resulted in a 55% increase in maximal phospholipid secretion compared with that in mice on the control diet. Northern blotting revealed that cholate feeding increased mdr2 Pgp mRNA levels by 42%. Feeding with ursodeoxycholate did not influence the maximum rate of phospholipid output or the mdr2 mRNA content. Female mice had a higher basal mdr2 Pgp mRNA level than male mice, and this was also correlated with a higher phospholipid secretion capacity. This could be explained by the 4-fold higher basal cholate content in the bile of female compared with male mice. Our results suggest that the type of bile salts in the circulation influences the expression of the mdr2 gene.

scholarly journals Passive Sorting in Maturing Granules of AtT-20 Cells: The Entry and Exit of Salivary Amylase and Proline-rich Protein

1997 ◽  
Vol 138 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Anna M. Castle ◽  
Amy Y. Huang ◽  
J. David Castle
Keyword(s):  
Secretory Pathway ◽  
Critical Role ◽  
Endogenous Hormones ◽  
Salivary Amylase ◽  
Regulated Secretion ◽  
J 13 ◽  
Regulated Secretory Pathway ◽  
Granule Maturation ◽  
Proline Rich Protein

Previous studies have suggested that salivary amylase and proline-rich protein are sorted differently when expressed in AtT-20 cells (Castle, A.M., L.E. Stahl, and J.D. Castle. 1992. J. Biol. Chem. 267:13093– 13100; Colomer, V., K. Lal, T.C. Hoops, and M.J. Rindler. 1994.EMBO (Eur. Mol. Biol. Organ.) J. 13:3711– 3719). We now show that both exocrine proteins behave similarly and enter the regulated secretory pathway as judged by immunolocalization and secretagogue- dependent stimulation of secretion. Analysis of stimulated secretion of newly synthesized proline-rich protein, amylase, and endogenous hormones indicates that the exogenous proteins enter the granule pool with about the same efficiency as the endogenous hormones. However, in contrast to the endogenous hormones, proline-rich protein and amylase are progressively removed from the granule pool during the process of granule maturation such that only small portions remain in mature granules where they colocalize with the stored hormones. The exogenous proteins that are not stored are recovered from the incubation medium and are presumed to have undergone constitutive-like secretion. These results point to a level of sorting for regulated secretion after entry of proteins into forming granules and indicate that retention is essential for efficient storage. Consequently, the critical role of putative sorting receptors for regulated secretion may be in retention rather than in granule entry.

scholarly journals PACS-1 and adaptor protein-1 mediate ACTH trafficking to the regulated secretory pathway

2018 ◽  
Vol 507 (1-4) ◽  
pp. 519-525 ◽  
Author(s):  
Brennan S. Dirk ◽  
Christopher End ◽  
Emily N. Pawlak ◽  
Logan R. Van Nynatten ◽  
Rajesh Abraham Jacob ◽  
...  
Keyword(s):  
Secretory Pathway ◽  
Adaptor Protein ◽  
Regulated Secretory Pathway

scholarly journals Sorting and storage during secretory granule biogenesis: looking backward and looking forward

1998 ◽  
Vol 332 (3) ◽  
pp. 593-610 ◽  
Author(s):  
Peter ARVAN ◽  
David CASTLE
Keyword(s):  
Secretory Pathway ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Secretory Proteins ◽  
Membrane Composition ◽  
Granule Formation ◽  
Granule Membrane ◽  
Regulated Secretory Pathway ◽  
Secretory Products

Secretory granules are specialized intracellular organelles that serve as a storage pool for selected secretory products. The exocytosis of secretory granules is markedly amplified under physiologically stimulated conditions. While granules have been recognized as post-Golgi carriers for almost 40 years, the molecular mechanisms involved in their formation from the trans-Golgi network are only beginning to be defined. This review summarizes and evaluates current information about how secretory proteins are thought to be sorted for the regulated secretory pathway and how these activities are positioned with respect to other post-Golgi sorting events that must occur in parallel. In the first half of the review, the emerging role of immature secretory granules in protein sorting is highlighted. The second half of the review summarizes what is known about the composition of granule membranes. The numerous similarities and relatively limited differences identified between granule membranes and other vesicular carriers that convey products to and from the plasmalemma, serve as a basis for examining how granule membrane composition might be established and how its unique functions interface with general post-Golgi membrane traffic. Studies of granule formation in vitro offer additional new insights, but also important challenges for future efforts to understand how regulated secretory pathways are constructed and maintained.

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