{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nanou E"],"funding":["NINDS NIH HHS"],"pagination":["504-513"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3249104"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["287(1)"],"pubmed_abstract":["CaV2.1 channels, which conduct P/Q-type Ca2+ currents, initiate synaptic transmission at most synapses in the central nervous system. Ca2+/calmodulin-dependent facilitation and inactivation of these channels contributes to short-term facilitation and depression of synaptic transmission, respectively. Other calcium sensor proteins displace calmodulin (CaM) from its binding site, differentially regulate CaV2.1 channels, and contribute to the diversity of short-term synaptic plasticity. The neuronal calcium sensor protein visinin-like protein 2 (VILIP-2) inhibits inactivation and enhances facilitation of CaV2.1 channels. Here we examine the molecular determinants for differential regulation of CaV2.1 channels by VILIP-2 and CaM by construction and functional analysis of chimeras in which the functional domains of VILIP-2 are substituted in CaM. Our results show that the N-terminal domain, including its myristoylation site, the central α-helix, and the C-terminal lobe containing EF-hands 3 and 4 of VILIP-2 are sufficient to transfer its regulatory properties to CaM. This regulation by VILIP-2 requires binding to the IQ-like domain of CaV2.1 channels. Our results identify the essential molecular determinants of differential regulation of CaV2.1 channels by VILIP-2 and define the molecular code that these proteins use to control short-term synaptic plasticity."],"journal":["The Journal of biological chemistry"],"pubmed_title":["Molecular determinants of modulation of CaV2.1 channels by visinin-like protein 2."],"pmcid":["PMC3249104"],"funding_grant_id":["R01 NS22625","R01 NS022625"],"pubmed_authors":["Martinez GQ","Catterall WA","Nanou E","Scheuer T"],"additional_accession":[]},"is_claimable":false,"name":"Molecular determinants of modulation of CaV2.1 channels by visinin-like protein 2.","description":"CaV2.1 channels, which conduct P/Q-type Ca2+ currents, initiate synaptic transmission at most synapses in the central nervous system. Ca2+/calmodulin-dependent facilitation and inactivation of these channels contributes to short-term facilitation and depression of synaptic transmission, respectively. Other calcium sensor proteins displace calmodulin (CaM) from its binding site, differentially regulate CaV2.1 channels, and contribute to the diversity of short-term synaptic plasticity. The neuronal calcium sensor protein visinin-like protein 2 (VILIP-2) inhibits inactivation and enhances facilitation of CaV2.1 channels. Here we examine the molecular determinants for differential regulation of CaV2.1 channels by VILIP-2 and CaM by construction and functional analysis of chimeras in which the functional domains of VILIP-2 are substituted in CaM. Our results show that the N-terminal domain, including its myristoylation site, the central α-helix, and the C-terminal lobe containing EF-hands 3 and 4 of VILIP-2 are sufficient to transfer its regulatory properties to CaM. This regulation by VILIP-2 requires binding to the IQ-like domain of CaV2.1 channels. Our results identify the essential molecular determinants of differential regulation of CaV2.1 channels by VILIP-2 and define the molecular code that these proteins use to control short-term synaptic plasticity.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Jan","modification":"2026-05-03T15:25:50.141Z","creation":"2019-03-27T00:47:31Z"},"accession":"S-EPMC3249104","cross_references":{"pubmed":["22074920"],"doi":["10.1074/jbc.m111.292581","10.1074/jbc.M111.292581"]}}