RGD Reference Report - Reduction of AP180 and CALM produces defects in synaptic vesicle size and density. - Rat Genome Database

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Reduction of AP180 and CALM produces defects in synaptic vesicle size and density.

Authors: Petralia, Ronald S  Wang, Ya-Xian  Indig, Fred E  Bushlin, Ittai  Wu, Fangbai  Mattson, Mark P  Yao, Pamela J 
Citation: Petralia RS, etal., Neuromolecular Med. 2013 Mar;15(1):49-60. doi: 10.1007/s12017-012-8194-x. Epub 2012 Aug 1.
RGD ID: 13506174
Pubmed: PMID:22851330   (View Abstract at PubMed)
PMCID: PMC3818133   (View Article at PubMed Central)
DOI: DOI:10.1007/s12017-012-8194-x   (Journal Full-text)

Clathrin assembly proteins AP180 and CALM regulate the assembly of clathrin-coated vesicles (CCVs), which mediate diverse intracellular trafficking processes, including synaptic vesicle (SV) recycling at the synapse. Although studies using several invertebrate model systems have indicated a role for AP180 in SV recycling, less is known about AP180's or CALM's function in the synapse of mammalian neurons. In this study, we examined synapses of rat hippocampal neurons in which the level of AP180 or CALM had been reduced by RNA interference (RNAi). Using light microscopy, we visualized synaptic puncta in these AP180- or CALM-reduced neurons by co-expressing Synaptophysin::EGFP (Syp::EGFP). We found that neurons with reduced AP180 or reduced CALM had smaller Syp::EGFP-illuminated puncta. Using electron microscopy, we further examined the ultrastructure of the AP180- or CALM-reduced presynaptic terminals. We found that SVs became variably enlarged in both the AP180-reduced and CALM-reduced presynaptic terminals. Lower AP180 and CALM also reduced the density of SVs and the size of SV clusters. Our findings demonstrate that in the presynaptic terminals of hippocampal neurons, AP180 and CALM have a similar role in regulating synaptic vesicles. This overlapping activity may be necessary for high-precision and high-efficacy SV formation during endocytosis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of synaptic vesicle clustering  IMP 13506174; 13506174 RGD 
regulation of terminal button organization  IMP 13506174; 13506174 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Picalm  (phosphatidylinositol binding clathrin assembly protein)
Snap91  (synaptosome associated protein 91)


Additional Information