Annexin 7 mobilizes calcium from endoplasmic reticulum stores in brain

Mobilization of intracellular calcium from inositol-1,4,5 -triphosphate (IP3)-sensitive endoplasmic reticulum (ER) stores plays a prominent role in brain function. Mice heterozygous for the annexin A7 (Anx7) gene have a profound reduction in IP3 receptor function in pancreatic islets along with defective insulin secretion. We examined IP3-sensitive calcium pools in the brains of Anx7 (+/-) mice by utilizing ATP/Mg2+-dependent Ca-45(2+) uptake into brain membrane preparations and tissue sections. Although the Anx7 (+/-) mouse brain displayed similar levels of IP3 binding sites and thapsigargin-sensitive Ca-45(2+) uptake as that seen in wild-type mouse brain, the Anx7 (+/-) mouse brain Ca2+ pools showed markedly reduced sensitivity to IP3. A potent and saturable Ca2+-releasing effect of recombinant ANX7 protein was demonstrated in mouse and rat brain membrane preparations, which was additive with that of IP3. We propose that ANX7 mobilizes Ca2+ from an endoplasmic reticulum-like pool, which can be recruited to enhance IP3-mediated Ca2+ release. (C) 2004 Elsevier B.V.All rights reserved.