Jaw1 controls the granule abundance at a distinct ER compartment of pancreatic acinar cells.

Pancreatic acinar cells (PACs) are specialized for the production and secretion of digestive enzymes. PACs are highly polarized, with rough endoplasmic reticulum (ER) located in the basal and lateral regions, while zymogen granules (ZG) are localized apically. Furthermore, a distinct ER compartment containing inositol 1,4,5-trisphosphate receptors (IP3Rs), which are Ca2+ channels, is positioned underneath the filamentous-actin and tight junctions in the apical region. This structurally polarized architecture underlies the localized elevation of Ca2+ levels in the apical region, which supports the efficient secretion of granules. In this report, we show that Jaw1, a regulatory protein of IP3Rs, is a new component of the distinct ER compartment in PACs, colocalizing with IP3R2 and IP3R3 rather than IP3R1. Importantly, PACs from Jaw1-deficient mice exhibited an accumulation of ZG and cell hypertrophy without disrupting both the arrangement of the distinct ER compartment and the localization of IP3Rs. These findings shed more light on the underlying molecular components of the distinct ER compartment in the apical region of PACs, offering insights into their physiological functions in the homeostatic control of ZG abundance in PACs.Key words: cell polarity, ER, IP3Rs, Jaw1, pancreatic acinar cells.