Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0004352 (
autism
)
32,579
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The tight spatial coupling of synaptic vesicles and voltage-gated Ca
2+
channels (Ca
V
s) ensures efficient action potential-triggered neurotransmitter release from presynaptic active zones (AZs). Rab-interacting molecule-binding proteins (RIM-BPs) interact with Ca
2+
channels and via RIM with other components of the release machinery. Although human RIM-BPs have been implicated in
autism
spectrum disorders, little is known about the role of mammalian RIM-BPs in synaptic transmission. We investigated RIM-BP2-deficient murine hippocampal neurons in cultures and slices. Short-term facilitation is significantly enhanced in both model systems. Detailed analysis in culture revealed a reduction in initial release probability, which presumably underlies the increased short-term facilitation. Superresolution microscopy revealed an impairment in Ca
V
2.1 clustering at AZs, which likely alters Ca
2+
nanodomains at release sites and thereby affects release probability. Additional deletion of
RIM-BP1
does not exacerbate the phenotype, indicating that RIM-BP2 is the dominating RIM-BP isoform at these synapses.
...
PMID:RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses. 2767 55
