Inositol 1,4,5-trisphosphate receptor/GAPDH complex augments Ca 2+ release via locally derived NADH

Randen L. Patterson; Damian B. Van Rossum; Adam I. Kaplin; Roxanne K. Barrow; Solomon H. Snyder

doi:10.1073/pnas.0409657102

Inositol 1,4,5-trisphosphate receptor/GAPDH complex augments Ca ²⁺ release via locally derived NADH

Randen L. Patterson, Damian B. Van Rossum, Adam I. Kaplin, Roxanne K. Barrow, Solomon H. Snyder

School of Medicine

Research output: Contribution to journal › Article › peer-review

70 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1357-1359
Number of pages	3
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	102
Issue number	5
DOIs	https://doi.org/10.1073/pnas.0409657102
State	Published - Feb 1 2005

Keywords

Calcium
Hypoxia
Metabolism

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.0409657102

Cite this

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title = "Inositol 1,4,5-trisphosphate receptor/GAPDH complex augments Ca 2+ release via locally derived NADH",

abstract = "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.",

keywords = "Calcium, Hypoxia, Metabolism",

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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.

KW - Calcium

KW - Hypoxia

KW - Metabolism

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