Calcium signalling in and around the nuclear envelope

Area of Science:

• Cellular Biology
• Molecular Physiology
• Calcium Signaling

Background:

• Calcium ions (Ca2+) are critical intracellular second messengers involved in numerous cellular processes.
• Inositol 1,4,5-trisphosphate (IP3), cyclic ADP-ribose (cADPR), and nicotinic acid-adenosine dinucleotide phosphate (NAADP) are key modulators of intracellular calcium release.
• The role of nuclear calcium stores in pancreatic acinar cells remains an area of active investigation.

Purpose of the Study:

• To compare the ability of IP3, cADPR, and NAADP to mobilize calcium from isolated pancreatic acinar nuclei.
• To investigate the characteristics of calcium stores within the nuclear envelope of pancreatic acinar cells.
• To determine if NAADP acts on the same calcium stores as IP3 and cADPR in these cells.

Main Methods:

• Utilized calcium-sensitive fluorescent probes to monitor Ca2+ uptake and release.
• Studied calcium mobilization from isolated pancreatic acinar nuclei and intact pancreatic acinar cells.
• Employed thapsigargin pre-treatment and various pharmacological tools to characterize calcium stores.

Main Results:

• All three calcium messengers (IP3, cADPR, and NAADP) induced Ca2+ release from the nuclear envelope.
• Nuclear Ca2+ stores were sensitive to thapsigargin, with pre-treatment abolishing responses to all messengers.
• Pharmacological evidence suggests pancreatic acinar nuclear Ca2+ release originates from stores with endoplasmic reticulum characteristics.

Conclusions:

• IP3, cADPR, and NAADP all mobilize Ca2+ from pancreatic acinar nuclear stores.
• These nuclear stores possess endoplasmic reticulum-like characteristics and are thapsigargin-sensitive.
• NAADP appears to release Ca2+ from the same IP3- and cADPR-sensitive stores within the nucleus.