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RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release

PNAS, 24 February 2004
Vol. 101, Issue 8, p. 2328-2332
DOI: 10.1073/pnas.0308567100

RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release

  1. Randen L. Patterson * , ,
  2. Damian B. van Rossum * , ,
  3. Roxanne K. Barrow *, and
  4. Solomon H. Snyder * , , § ,
  1. Departments of *Neuroscience, Pharmacology and Molecular Science, and §Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205
  1. Contributed by Solomon H. Snyder, December 30, 2003


RACK1 is not a G protein but closely resembles the heterotrimeric Gβ-subunit. RACK1 serves as a scaffold, linking protein kinase C to its substrates. We demonstrate that RACK1 physiologically binds inositol 1,4,5-trisphosphate receptors and regulates Ca2+ release by enhancing inositol 1,4,5-trisphosphate receptor binding affinity for inositol 1,4,5-trisphosphate. Overexpression of RACK1 or depletion of RACK1 by interference RNA markedly augments or diminishes Ca2+ release, respectively, without affecting Ca2+ entry. These findings establish RACK1 as a physiologic mediator of agonist-induced Ca2+ release.


  • To whom correspondence should be addressed at: Department of Neuroscience, Johns Hopkins University, 725 North Wolfe Street, 813 WBSB, Baltimore, MD 21205. E-mail: ssnyder{at}

  • R.L.P. and D.B.v.R. contributed equally to this work.

  • Abbreviations: IP3, inositol 1,4,5-trisphosphate; IP3R, IP3 receptor; Gβ, Gβ-subunit; siRNA, small interfering RNA; YFP, yellow fluorescent protein; aa, amino acids; HEK, human embryonic kidney.


R. L. Patterson, D. B. van Rossum, R. K. Barrow, and S. H. Snyder, RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release. PNAS 101, 2328-2332 (2004).

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