Organelle Selection Determines Agonist-specific Ca2+ Signals in Pancreatic Acinar and β Cells

Michiko Yamasaki,Roser Masgrau,Anthony J Morgan,Grant C Churchill,Sandip Patel,Stephen J.H Ashcroft,Antony Galione

doi:10.1074/jbc.m311088200

Michiko Yamasaki, Roser Masgrau + Show 5 more

Open Access

https://doi.org/10.1074/jbc.m311088200

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Abstract

How different extracellular stimuli can evoke different spatiotemporal Ca2+ signals is uncertain. We have elucidated a novel paradigm whereby different agonists use different Ca2+-storing organelles ("organelle selection") to evoke unique responses. Some agonists select the endoplasmic reticulum (ER), and others select lysosome-related (acidic) organelles, evoking spatial Ca2+ responses that mirror the organellar distribution. In pancreatic acinar cells, acetylcholine and bombesin exclusively select the ER Ca2+ store, whereas cholecystokinin additionally recruits a lysosome-related organelle. Similarly, in a pancreatic beta cell line MIN6, acetylcholine selects only the ER, whereas glucose mobilizes Ca2+ from a lysosome-related organelle. We also show that the key to organelle selection is the agonist-specific coupling messenger(s) such that the ER is selected by recruitment of inositol 1,4,5-trisphosphate (or cADP-ribose), whereas lysosome-related organelles are selected by NAADP.

Highlights

How different extracellular stimuli can evoke different spatiotemporal Ca2؉ signals is uncertain
We show that the key to organelle selection is the agonist-specific coupling messenger(s) such that the endoplasmic reticulum (ER) is selected by recruitment of inositol 1,4,5-trisphosphate, whereas lysosome-related organelles are selected by nicotinic acid adenine dinucleotide phosphate (NAADP)
It has become clear that a primary factor governing agonist specificity is the release of Ca2ϩ from intracellular stores, a process that encompasses multiple channel families regulated by the second messengers inositol 1,4,5-trisphosphate (IP3), cyclic ADP-ribose, and nicotinic acid adenine dinucleotide phosphate (NAADP)

Summary

Introduction

How different extracellular stimuli can evoke different spatiotemporal Ca2؉ signals is uncertain. Acetylcholine and bombesin exclusively select the ER Ca2؉ store, whereas cholecystokinin recruits a lysosome-related organelle.

Results

Conclusion