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,¶
* Center for Biomedical Research at The Queen’s Medical Center, Honolulu, HI 96813;
Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96813;
Pacific Bioscience Research Center, University of Hawaii, Honolulu, HI 96922;
Graduate Program in Microbiology, University of Hawaii, Honolulu, HI 96822; and
¶ Program in Molecular Biosciences and Bioengineering, University of Hawaii, Honolulu, HI 96822
Mast cells are granular immunocytes that reside in the body’s barrier tissues. These cells orchestrate inflammatory responses. Proinflammatory mediators are stored in granular structures within the mast cell cytosol. Control of mast cell granule exocytosis is a major therapeutic goal for allergic and inflammatory diseases. However, the proteins that control granule biogenesis and abundance in mast cells have not been elucidated. In neuroendocrine cells, whose dense core granules are strikingly similar to mast cell granules, granin proteins regulate granulogenesis. Our studies suggest that the Secretogranin III (SgIII) protein is involved in secretory granule biogenesis in mast cells. SgIII is abundant in mast cells, and is organized into vesicular structures. Our results show that over-expression of SgIII in mast cells is sufficient to cause an expansion of a granular compartment in these cells. These novel granules store inflammatory mediators that are released in response to physiological stimuli, indicating that they function as bona fide secretory vesicles. In mast cells, as in neuroendocrine cells, we show that SgIII is complexed with Chromogranin A (CgA). CgA is granulogenic when complexed with SgIII. Our data show that a novel non-granulogenic truncation mutant of SgIII (1–210) lacks the ability to interact with CgA. Thus, in mast cells, a CgA-SgIII complex may play a key role in secretory granule biogenesis. SgIII function in mast cells is unlikely to be limited to its partnership with CgA, as our interaction trap analysis suggests that SgIII has multiple binding partners, including the mast cell ion channel TRPA1.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Leahi Fund for Pulmonary Research (awards to H.T. and A.J.S.), McKee Fund (to A.J.S.), NIH RO1 GM 070634 (to H.T.) and NCRR INBRE P20RR016467 (sub-award to H.T.).
2 Current affiliations: H.T., Chaminade University of Honolulu; A.J.S., Center for Cardiovascular Research, John. A. Burns School of Medicine, University of Hawaii; P.P., Institute for Biogenesis Research, John. A. Burns School of Medicine, University of Hawaii; A. S.-H., AMDL, Tustin, CA.
3 Address correspondence and reprint requests to Dr. Helen Turner, Castle Science Center 116, Chaminade University, 3140 Waialae Avenue, Honolulu HI 96816. E-mail address: hturner{at}chaminade.edu or astokes{at}hawaii.edu
4 Abbreviations used in this paper: CgA, chromogranin A; CgB, chromogranin B; Sg, secretogranin; w/v, weight-to-volume ratio; RT, room temperature.
This article has been cited by other articles:
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  S. Paco, E. Pozas, and F. Aguado Secretogranin III Is an Astrocyte Granin That Is Overexpressed in Reactive Glia Cereb Cortex, November 5, 2009; (2009) bhp202v1. [Abstract] [Full Text] [PDF]
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