TY - JOUR
T1 - Inositol 1,4,5-trisphosphate receptor/GAPDH complex augments Ca 2+ release via locally derived NADH
AU - Patterson, Randen L.
AU - Van Rossum, Damian B.
AU - Kaplin, Adam I.
AU - Barrow, Roxanne K.
AU - Snyder, Solomon H.
PY - 2005/2/1
Y1 - 2005/2/1
N2 - NADH regulates the release of calcium from the endoplasmic reticulum by modulation of inositol 1,4,5-trisphosphate receptors (IP3R), accounting for the augmented calcium release of hypoxic cells. We report selective binding of IP3R to GAPDH, whose activity leads to the local generation of NADH to regulate intracellular calcium signaling. This interaction requires cysteines 992 and 995 of IP3R and C150 of GAPDH. Addition of native GAPDH and NAD+ to WT IP3R stimulates calcium release, whereas no stimulation occurs with C992S/995S IP3R that cannot bind GAPDH. Thus, the IP3R/GAPDH interaction likely enables cellular energy dynamics to impact calcium signaling.
AB - NADH regulates the release of calcium from the endoplasmic reticulum by modulation of inositol 1,4,5-trisphosphate receptors (IP3R), accounting for the augmented calcium release of hypoxic cells. We report selective binding of IP3R to GAPDH, whose activity leads to the local generation of NADH to regulate intracellular calcium signaling. This interaction requires cysteines 992 and 995 of IP3R and C150 of GAPDH. Addition of native GAPDH and NAD+ to WT IP3R stimulates calcium release, whereas no stimulation occurs with C992S/995S IP3R that cannot bind GAPDH. Thus, the IP3R/GAPDH interaction likely enables cellular energy dynamics to impact calcium signaling.
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U2 - 10.1073/pnas.0409657102
DO - 10.1073/pnas.0409657102
M3 - Article
C2 - 15677321
AN - SCOPUS:13444255991
SN - 0027-8424
VL - 102
SP - 1357
EP - 1359
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -