Is a sorting signal necessary to package proteins into secretory granules?

Reaves, Barbara J.; Dannies, Priscilla S.

doi:10.1016/0303-7207(91)90085-7

Cited by 23 publications

(14 citation statements)

References 40 publications

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“…For example, growth hormone, prolactin, and chromogranins are sorted to the regulated secretory pathway although none of these are processed by proteolysis. It has been suggested that such proteins may be sorted/retained in secretory granules by a process of selective aggregation (36). Others, such as atrial natriuretic factor, appear to aggregate in the immature secretory granules as a prohormone and are processed upon release of the mature secretory granule (5,37).…”

Section: Discussionmentioning

confidence: 99%

A Protease Processing Site Is Essential for Prorenin Sorting to the Regulated Secretory Pathway

Brechler

Chu

Baxter

et al. 1996

Journal of Biological Chemistry

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Transfected mouse pituitary AtT-20 cells were used to examine the sorting of human prorenin to dense core secretory granules and the regulated secretory pathway. These cells secrete prorenin constitutively and sort a portion of the prorenin to secretory granules, where it is converted to active renin by proteolytic processing. Pulse-chase labeling of transfected AtT-20 cells demonstrated that regulated secretion of prorenin was prevented by: 1) the mutagenic deletion of the prosegment, 2) the premature proteolytic removal of the prosegment by a Golgi-resident processing protease, or 3) the mutation of the native cleavage site so as to prevent removal of the prosegment. In addition, expression of fusion proteins containing portions of the prorenin prosegment demonstrated that exposure of potential proteolytic cleavage sites was sufficient to confer cleavage-dependent regulated secretion of the corresponding protein. These data implicate the protease cleavage event in the regulated secretion of prorenin and are consistent with the involvement of a subclass of processing proteases in the sorting of certain proteins to secretory granules in AtT-20 cells.

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Section: Discussionmentioning

confidence: 99%

A Protease Processing Site Is Essential for Prorenin Sorting to the Regulated Secretory Pathway

Brechler

Chu

Baxter

et al. 1996

Journal of Biological Chemistry

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“…B, S1 nuclease assay for human and mouse SP-B mRNA. Total RNA from transgenic mice and control wild type littermates from two lines (line 6.1, lanes 1-4, and line 7.6, lanes [5][6][7][8] were assessed for hSP-B and mSP-B mRNA using 32 P-end-labeled, linearized hSP-B probe that protects a 169-nucleotide fragment in exons 5-7 and a mSP-B probe that protects a 186-nucleotide fragment. Ribosomal L32 (400 nucleotide) was used to normalize for loading.…”

Section: Discussionmentioning

confidence: 99%

“…The coexistence of constitutive and regulated secretory pathways within the same cell implies that segregation of proteins must occur, a process which is believed to take place in the trans-Golgi network (3)(4)(5)(6). Previous studies have identified selective aggregation and interaction of proteins with the membrane of the trans-Golgi network as important elements in the sorting of proteins away from the constitutive pathway and into the regulated secretory pathway (7)(8)(9)(10). To date no sorting receptor has been conclusively identified; however, the ability of different cell types to target heterologous proteins to the regulated secretory pathway supports the existence of a common sorting mechanism (2).…”

mentioning

confidence: 95%

Structural Requirements for Targeting of Surfactant Protein B (SP-B) to Secretory Granules in Vitro and in Vivo

Lin

Akinbi

Breslin

et al. 1996

Journal of Biological Chemistry

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Proteins reach their extracellular destination by one of two distinct secretory pathways: the constitutive secretory pathway, common to all mammalian cells, is the default pathway in which proteins are rapidly released from the cell by exocytosis; the regulated secretory pathway, present in certain cell types such as neuronal, endocrine, and exocrine cells, is characterized by storage of selected proteins in secretory granules which are released in response to appropriate external stimuli (1, 2). The coexistence of constitutive and regulated secretory pathways within the same cell implies that segregation of proteins must occur, a process which is believed to take place in the trans-Golgi network (3-6). Previous studies have identified selective aggregation and interaction of proteins with the membrane of the trans-Golgi network as important elements in the sorting of proteins away from the constitutive pathway and into the regulated secretory pathway (7-10). To date no sorting receptor has been conclusively identified; however, the ability of different cell types to target heterologous proteins to the regulated secretory pathway supports the existence of a common sorting mechanism (2). Sorting signals recognized by the putative receptor(s) are not encoded in the primary sequence of secretory proteins but are comprised of a motif(s) generated by higher order structure of the molecule (2, 11). Such a sorting signal has recently been identified for chromogranin B and shown to consist of a 20-amino acid loop stabilized by an intramolecular disulfide bond (12, 13).The alveolar type II epithelial cell is a specialized exocrine cell, which synthesizes and secretes pulmonary surfactant, a complex mixture of phospholipids and proteins required for maintenance of alveolar patency. Both the lipid and protein components of surfactant are stored in secretory granules (lamellar bodies), which are released by exocytosis in response to secretagogue stimulation (14, 15). The regulated secretory pathway of the type II cell is atypical in that the lamellar body compartment communicates extensively with the endocytic pathway; up to 85% of surfactant lipids are recycled to the lamellar body for resecretion (16). A further unique characteristic of lamellar bodies is the lysosomal nature of this compartment, including hydrolytic enzymes (17) and at least one lysosomal membrane glycoprotein (18). Sorting determinants mediating the selective transport of secretory proteins to the lamellar body have not been studied previously, and it is consequently unclear if these determinants act in a cell-specific manner. The purpose of the present study was to identify peptide domains required for targeting SP-B 1 to the lamellar body and to determine if these targeting epitopes are recognized by the sorting machinery of both endocrine and neuronal cells.Human SP-B is synthesized by the alveolar type II epithelial cell as a preproprotein of 381 amino acids. Within the proprotein the 79-residue mature peptide is flanked by propeptides of 177 and 10...

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“…One model is that a 'sorting signal' exists on regulated secretory proteins allowing them to bind to the membrane of nascent immature secretory granules and be included in them [73]. Another model is that selective co-aggregation of regulated proteins allows their inclusion in nascent immature secretory vesicles based on membrane envelopment of aggregates of characteristic size, and independent of specific interactions between secreted proteins and secretory granule membranes [74]. CGA may mediate sorting to the regulated pathway by both mechanisms.…”

Section: Chromogranin A: Aggregatory Properties and Their Relevance Tmentioning

confidence: 99%

Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway

Iacangelo

Eiden

1995

Regulatory Peptides

165

115

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Is a sorting signal necessary to package proteins into secretory granules?

Cited by 23 publications

References 40 publications

A Protease Processing Site Is Essential for Prorenin Sorting to the Regulated Secretory Pathway

A Protease Processing Site Is Essential for Prorenin Sorting to the Regulated Secretory Pathway

Structural Requirements for Targeting of Surfactant Protein B (SP-B) to Secretory Granules in Vitro and in Vivo

Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway

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