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 PMID:29123133  

AIP limits neurotransmitter release by inhibiting calcium bursts from the ryanodine receptor.

Bojun Chen | Ping Liu | Edward J Hujber | Yan Li | Erik M Jorgensen | Zhao-Wen Wang
Nature communications | 2017

Pituitary tumors are frequently associated with mutations in the AIP gene and are sometimes associated with hypersecretion of growth hormone. It is unclear whether other factors besides an enlarged pituitary contribute to the hypersecretion. In a genetic screen for suppressors of reduced neurotransmitter release, we identified a mutation in Caenorhabditis elegans AIPR-1 (AIP-related-1), which causes profound increases in evoked and spontaneous neurotransmitter release, a high frequency of spontaneous calcium transients in motor neurons and an enlarged readily releasable pool of vesicles. Calcium bursts and hypersecretion are reversed by mutations in the ryanodine receptor but not in the voltage-gated calcium channel, indicating that these phenotypes are caused by a leaky ryanodine receptor. AIPR-1 is physically associated with the ryanodine receptor at synapses. Finally, the phenotypes in aipr-1 mutants can be rescued by presynaptic expression of mouse AIP, demonstrating that a conserved function of AIP proteins is to inhibit calcium release from ryanodine receptors.

Pubmed ID: 29123133

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM113004
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH085927
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS034307
  • Agency: Howard Hughes Medical Institute, United States

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