ArticleMolecular biology of the cell1995
Ionic milieu controls the compartment-specific activation of pro-opiomelanocortin processing in AtT-20 cells.
Article in Molecular biology of the cell, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 72 citations in OpenAlex.
- FLIM-Based Intracellular and Extracellular pH Measurements Using Genetically Encoded pH Sensor.Biosensors · 2021Article
- Overcoming Chemoresistance: Altering pH of Cellular Compartments by Chloroquine and Hydroxychloroquine.Frontiers in cell and developmental biology · 2021Review
- Janus sword actions of chloroquine and hydroxychloroquine against COVID-19.Cellular signalling · 2020Article
- Article
- O-Glycosylation of a Secretory Granule Membrane Enzyme Is Essential for Its Endocytic Trafficking.The Journal of biological chemistry · 2016Article
- Biochemical and cell biological properties of the human prohormone convertase 1/3 Ser357Gly mutation: a PC1/3 hypermorph.Endocrinology · 2014Article
- A three-stage model of Golgi structure and function.Histochemistry and cell biology · 2013Review
- V-ATPase-mediated granular acidification is regulated by the V-ATPase accessory subunit Ac45 in POMC-producing cells.Molecular biology of the cell · 2010Article
- Inhibitors of the V0 subunit of the vacuolar H+-ATPase prevent segregation of lysosomal- and secretory-pathway proteins.Journal of cell science · 2009Article
- Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Prothyrotropin-releasing hormone targets its processing products to different vesicles of the secretory pathway.The Journal of biological chemistry · 2008Article
- Sending proteins to dense core secretory granules: still a lot to sort out.The Journal of cell biology · 2007Review
- PMR1/SPCA Ca2+ pumps and the role of the Golgi apparatus as a Ca2+ store.Pflugers Archiv : European journal of physiology · 2003Review
- Biogenesis of regulated exocytotic carriers in neuroendocrine cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2000Article
- Proinsulin endoproteolysis confers enhanced targeting of processed insulin to the regulated secretory pathway.Molecular biology of the cell · 2000Article
- Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with green fluorescent proteins.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Distinct molecular events during secretory granule biogenesis revealed by sensitivities to brefeldin A.Molecular biology of the cell · 1997Article
- Characterization of the Golgi complex cleared of proteins in transit and examination of calcium uptake activities.Molecular biology of the cell · 1997Article
- pH-insensitive glucose indicators.Biotechnology progressArticle
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Newly synthesized prohormones and their processing enzymes transit through the same compartments before being packaged into regulated secretory granules. Despite this coordinated intracellular transport, prohormone processing does not occur until late in the secretory pathway. In the mouse pituitary AtT-20 cell line, conversion of pro-opiomelanocortin (POMC) to mature adrenocorticotropic hormone involves the prohormone convertase PC1. The mechanism by which this proteolytic processing is restricted to late secretory compartments is unknown; PC1 activity could be regulated by compartment-specific activators/inhibitors, or through changes in the ionic milieu that influence its activity. By arresting transport in a semi-intact cell system, we have addressed whether metabolically labeled POMC trapped in early secretory compartments can be induced to undergo conversion if the ionic milieu in these compartments is experimentally manipulated. Prolonged incubation of labeled POMC trapped in the endoplasmic reticulum or Golgi/trans-Golgi network did not result in processing, thereby supporting the theory that processing is normally a post-Golgi/trans-Golgi network event. However, acidification of these compartments allowed effective processing of POMC to the intermediate and mature forms. The observed processing increased sharply at a pH below 6.0 and required millimolar calcium, regardless of the compartment in which labeled POMC resided. These conditions also resulted in the coordinate conversion of PC1 from the 84/87 kDa into the 74-kDa and 66-kDa forms. We propose that POMC processing is predominantly restricted to acidifying secretory granules, and that a change in pH within these granules is both necessary and sufficient to activate POMC processing.
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