Journal article
Chromogranin B regulates early-stage insulin granule trafficking from the Golgi in pancreatic islet β-cells
Journal of cell science, Vol.132(13), jcs231373
07/01/2019
DOI: 10.1242/jcs.231373
PMCID: PMC6633396
PMID: 31182646
Abstract
Chromogranin B (CgB, also known as CHGB) is abundantly expressed in dense core secretory granules of multiple endocrine tissues and has been suggested to regulate granule biogenesis in some cell types, including the pancreatic islet β-cell, though the mechanisms are poorly understood. Here, we demonstrate a critical role for CgB in regulating secretory granule trafficking in the β-cell. Loss of CgB impairs glucose-stimulated insulin secretion, impedes proinsulin processing to yield increased proinsulin content, and alters the density of insulin-containing granules. Using an
in situ
fluorescent pulse-chase strategy to track nascent proinsulin, we show that loss of CgB impairs Golgi budding of proinsulin-containing secretory granules, resulting in a substantial delay in trafficking of nascent granules to the plasma membrane with an overall decrease in total plasma membrane-associated granules. These studies demonstrate that CgB is necessary for efficient trafficking of secretory proteins into the budding granule, which impacts the availability of insulin-containing secretory granules for exocytic release.
This article has an associated First Person interview with the first author of the paper.
Summary:
A novel fluorescent pulse-chase technology is used to demonstrate that CgB regulates granule budding in the islet β-cell.
Details
- Title: Subtitle
- Chromogranin B regulates early-stage insulin granule trafficking from the Golgi in pancreatic islet β-cells
- Creators
- Shelby C. Bearrows - University of IowaCasey J. Bauchle - University of IowaMcKenzie Becker - University of IowaJonathan M. Haldeman - Duke Medical CenterSvetha Swaminathan - University of IowaSamuel B. Stephens - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.132(13), jcs231373
- Publisher
- The Company of Biologists Ltd
- DOI
- 10.1242/jcs.231373
- PMID
- 31182646
- PMCID
- PMC6633396
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Grant note
- ; DK099294 / ;
- Language
- English
- Date published
- 07/01/2019
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359668002771
Metrics
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