Calexcitin interaction with neuronal ryanodine receptors

Thomas J. Nelson, Wei Qin Zhao, Shauna Yuan, Antonella Favit, Lucas Pozzo-Miller, Daniel L. Alkon

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Calexcitin (CE), a Ca2+ and GTP-binding protein, which is phosphorylated during memory consolidation, is shown here to co-purify with ryanodine receptors (RyRs) and bind to RyRs in a calcium-dependent manner. Nanomolar concentrations of CE released up to 46% of the 45Ca label from microsomes preloaded with 45CaCl2. This release was Cast-dependent and was blocked by antibodies against the RyR or CE, by the RyR inhibitor dantrolene, and by a seven-amino-acid peptide fragment corresponding to positions 4689-4697 of the RyR, but not by heparin, an Ins(1,4,5)P3-receptor antagonist. Anti-CE antibodies, in the absence of added CE, also blocked Ca2+ release elicited by ryanodine, suggesting that the CE and ryanodine binding sites were in relative proximity. Calcium imaging with bis-fura-2 after loading CE into hippocampal CA1 pyramidal cells in hippocampal slices revealed slow, local calcium transients independent of membrane depolarization. Calexcitin also released Ca2+ from liposomes into which purified RyR had been incorporated, indicating that CE binding can be a proximate cause of Ca2+ release. These results indicated that CE bound to RyRs and suggest that CE may be an endogenous modulator of the neuronal RyR.

Original languageEnglish (US)
Pages (from-to)423-433
Number of pages11
JournalBiochemical Journal
Issue number2
StatePublished - Jul 15 1999
Externally publishedYes


  • Calcium channels
  • Calcium-binding proteins
  • Liposomes
  • Memory
  • Squid

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