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/Mg(2+)-dependent (45)Ca(2+) uptake into brain membrane preparations and tissue sections. Although the Anx7 (+/-) mouse brain displayed similar levels of IP3 binding sites and thapsigargin-sensitive (45)Ca(2+) uptake as that seen in wild-type mouse brain, the Anx7 (+/-) mouse brain Ca(2+) pools showed markedly reduced sensitivity to IP3. A potent and saturable Ca(2+)-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 Ca(2+) from an endoplasmic reticulum-like pool, which can be recruited to enhance IP3-mediated Ca(2+) release.
Watson
W D
WD
Neurology Department, National Naval Medical Center, Bethesda, MD 20814, USA.
Srivastava
M
M
Leighton
X
X
Glasman
M
M
Faraday
M
M
Fossam
L H
LH
Pollard
H B
HB
Verma
A
A
D000818:Animals; D017310:Annexin A7 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley
D017310:Annexin A7; D017931:DNA Primers; D002118:Calcium