Matches in SemOpenAlex for { <https://semopenalex.org/work/W2133485771> ?p ?o ?g. }
- W2133485771 abstract "The conserved Ca2+-binding protein Frequenin/Neuronal Calcium Sensor 1 (Frq/NCS-1) is involved in pathologies that result from abnormal synapse number and probability of neurotransmitter release per synapse. Both synaptic features are likely co-regulated but the intervening mechanisms remain poorly understood. We show here that Drosophila Ric8a/Synembryn, a receptor-independent activator of G protein complexes, binds Frq2 but not the virtually identical duplicate Frq1. Based on crystallographic data on Frq2 and site directed mutagenesis on Frq1, the differential amino acids R94 and T138 account for this specificity. Human NCS-1 and Ric8a reproduce the binding and maintain the structural requirements at these key positions. Ric8a and Gαs regulate synapse number and neurotransmitter release and both are functionally linked to Frq2. Frq2 negatively regulates Ric8a to control synapse number. However, the regulation of neurotransmitter release by Ric8a is independent from the Frq2 binding. Thus, the antagonistic regulation of these two synaptic properties shares a common pathway, Frq2,Ric8a,Gαs which diverges downstream. These mechanisms expose the Frq2-Ric8a interacting surface as a potential pharmacological target for NCS-1 related diseases and provide key data towards the corresponding drug design." @default.
- W2133485771 created "2016-06-24" @default.
- W2133485771 creator A5006727146 @default.
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- W2133485771 date "2014-01-01" @default.
- W2133485771 modified "2023-10-02" @default.
- W2133485771 title "The guanine-exchange factor Ric8a binds the calcium sensor NCS-1 to regulate synapse number and probability of release" @default.
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- W2133485771 doi "https://doi.org/10.1242/jcs.152603" @default.
- W2133485771 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25074811" @default.
- W2133485771 hasPublicationYear "2014" @default.
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