Background: FKBP38 regulates the biogenesis of plasma membrane ion channels. Results: FKBP38 inhibits protein synthesis through its membrane anchorage and promotes CFTR post-translational folding through its PPIase domain, both negatively regulated by Hsp90 through the tetratricopeptide repeat domain. Conclusion: FKBP38 PPIase plays an important role in CFTR biogenesis. Significance: Our findings demonstrate an independent contribution of FKBP38 to CFTR biogenesis.

Background: Hsp105 prevents protein aggregation, accelerates Hsc70 nucleotide exchange, and functionally relates to Hsp90. Results: Hsp105 facilitates CFTR quality control coincident with translation, enhances its post-translational folding, and stabilizes misfolded CFTR at cell periphery. Conclusion: Hsp105 is a versatile regulator in CFTR folding and quality control. Significance: Hsp105 plays distinct roles in CFTR folding from other Hsc70 nucleotide exchange factors.

Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca 2؉ mobilizing second messenger discovered to date, has been implicated in Ca 2؉ signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca

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Key points• There are two major ionotropic purinoceptor subtypes (ATP-gated, non-selective, Ca 2+ -conducting ion channels) in the salivary gland.• Relatively little is known about the physiological roles of these purinoceptors regarding compartmentalization and selective activation, their contributions to the spatiotemporal properties of intracellular Ca 2+ signals and their roles in regulating protein exocytosis and ion channel activity.• In this study, we investigated the subtype-specific sub-cellular distribution and functional characterization of purinoceptors in mouse parotid acinar cells.• Selective activation of ionotropic purinergic receptor subtypes was shown to evoke spatially distinct cytosolic Ca 2+ signals as well as protein exocytosis.• This study identifies a subtype of ionotropic purinergic receptors as a potential therapeutic target for treatment of salivary gland hypofunction.Abstract There is emerging consensus that P2X 4 and P2X 7 ionotropic purinoceptors (P2X 4 R and P2X 7 R) are critical players in regulating [Ca 2+ ] i dynamics and fluid secretion in the salivary gland. In contrast, details regarding their compartmentalization and selective activation, contributions to the spatiotemporal properties of intracellular signals and roles in regulating protein exocytosis and ion channel activity have remained largely undefined. To address these concerns, we profiled mouse parotid acinar cells using live-cell imaging to follow the spatial and temporal features of ATP-evoked Ca 2+ dynamics and exocytotic activity. Selective activation of P2X 7 Rs revealed an apical-to-basal [Ca 2+ ] i signal that initiated at the sub-luminal border and propagated with a wave speed estimated at 17.3 ± 4.3 μm s −1 (n = 6). The evoked Ca 2+ spike consisted of Ca 2+ influx and Ca 2+ -induced Ca 2+ release from intracellular Ca 2+ channels. In contrast, selective activation of P2X 4 Rs induced a Ca 2+ signal that initiated basally and propagated toward the lumen with a wave speed of 4.3 ± 0.2 μm s −1 (n = 8) that was largely independent of intracellular Ca 2+ channel blockade. Consistent with these observations, P2X 7 R expression was enriched in the sub-luminal regions of acinar cells while P2X 4 R appeared localized to basal areas. In addition, we showed that P2X 4 R and P2X 7 R activation evokes exocytosis in parotid acinar cells. Our studies also demonstrate that the P2X 4 R-mediated [Ca 2+ ] i rise and subsequent protein exocytosis was enhanced by ivermectin (IVR). Thus, in addition to furthering our understanding of salivary gland physiology, this study identifies P2X 4 R as a potential target for treatment of salivary hypofunction diseases.