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

Mechanical forces play critical roles in tissue morphogenesis and homeostasis, yet how tissue mechanics are translated into epithelial cell delamination remains poorly understood. Here, we use the Drosophila pupal wing as an in vivo model to examine how release of tissue tension influences cell death and delamination. Surgical severing of the wing hinge or loss of dumpy (dpy) function alters the force distribution, promotes cell crowding, and thereby significantly increases epithelial cell delamination compared to wild-type controls. An RNAi analysis targeting mechanosensitive components identified Vinculin, an adherens junction–associated force adaptor, as a key suppressor of mechanically induced cell delamination. Both tissue tension release and Vinculin depletion reduced junctional Vinculin levels and elevated Notch transcriptional activity, while canonical Notch transcriptional activation remained undetectable within delaminating cells. In contrast, knockdown of the Notch ligand Delta suppressed cell death and delamination. These findings indicate that release of tissue tension causes changes in forces acting on cells and cell crowding, thereby altering Vinculin-dependent regulation of Delta–Notch signaling and promoting cell delamination through a non-canonical Notch pathway.

Key words: cell delamination, mechanotransduction, Delta–Notch pathways