Comparison of localization and release of multivesicular bodies and secretory granules in islet cells: Dysregulation during type-2 diabetes

Veerabhadraswamy, P and Lata, K and Dey, S and Belekar, P and Kothegala, L and Mangala Prasad, V and Gandasi, NR (2024) Comparison of localization and release of multivesicular bodies and secretory granules in islet cells: Dysregulation during type-2 diabetes. In: Journal of Extracellular Biology, 3 (11).

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Abstract

Multivesicular bodies (MVBs) are vesicles of endosomal origin containing intraluminal vesicles, which upon fusion with plasma membrane, secrete exosomes. They play a significant role in the physiology and pathology of type-2 diabetes (T2D) due to disrupted intercellular communication. The role of MVBs and their influence on insulin secretory granules (ISGs) of β-cells or their characterization is yet to be uncovered. In our study, we compared MVBs to largely well-characterized ISGs in β-cells. This study compares the density, localization, and exocytosis of CD63+ compartments (CD63+c) with NPY labelled ISGs (NISGs) in β-cells. For this, tetraspanin CD63 was exploited to majorly label MVBs in β-cells. These labels preserve the structural integrity of labelled compartments and mostly do not localize with other endo-lysosomal compartments. This study showed that the β-cells have a significantly higher density of NISGs than CD63+c. CD63+c and NISGs are spatially localized apart within β-cells. The proteins that localize with CD63+c are different from the ones that localize with NISGs. Exocytosis of NISGs occurs at the periphery of the β-cells and takes significantly less time when compared to the release of CD63+c, which is non-peripheral and takes a longer duration. Mechanistically, the availability of CD63+c for exocytosis was assessed and found that an equilibrium is maintained between docking and undocking states at the plasma membrane. Although there are a high number of short-term residing, visiting CD63+c at the plasma membrane, the availability of CD63+c for exocytosis is maintained due to docking and undocking states. Further, a significant reduction in the density of NISGs and CD63+c was observed in β-cells isolated from T2D donors compared to healthy counterparts. Studying the effect of MVBs on insulin secretion in physiological and T2D conditions has huge potential. This study provides a strong basis to open new avenues for such future studies. © 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

Item Type:	Journal Article
Publication:	Journal of Extracellular Biology
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to authors.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Biological Sciences > Centre for Infectious Disease Research
Date Deposited:	17 Dec 2024 05:50
Last Modified:	17 Dec 2024 05:50
URI:	http://eprints.iisc.ac.in/id/eprint/87129

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