Presenilin and Calcium Channel Regulation

Science's STKE  16 May 2000:
Vol. 2000, Issue 32, pp. tw2
DOI: 10.1126/stke.2000.32.tw2

Disruption of intracellular calcium homeostasis is a consequence of some mutations that arise in the integral membrane protein presenilin 2 (PS2) in familial Alzheimer's disease (FAD). Pack-Chung et al. report that a hydrophilic loop region of PS2 interacts with sorcin, a cytoplasmic calcium-binding protein that modulates the ryanodine receptor intracellular calcium channel. Sorcin-PS2 complexes were isolated from human brain tissue, and an increase in intracellular calcium stimulated sorcin translocation to membranes and sorcin-PS2 interaction in cultured cells. The authors suggest that sorcin, PS2, and the ryanodine receptor may comprise a molecular complex that modulates intracellular calcium and may thus play a role in FAD pathology.

Pack-Chung, E., Meyers, M.B., Pettingell, W.P., Moir, R.D., Brownawell, A.M., Cheng, I., Tanzi, R.E., and Kim, T.-W. (2000) Presenilin 2 interacts with sorcin, a modulator of the ryanodine receptor. J. Biol. Chem. 275: 14440-14445. [Abstract] [Full Text]