RGD Reference Report - Calcineurin Agamma is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis. - Rat Genome Database

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Calcineurin Agamma is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis.

Authors: Cottrell, JR  Li, B  Kyung, JW  Ashford, CJ  Mann, JJ  Horvath, TL  Ryan, TA  Kim, SH  Gerber, DJ 
Citation: Cottrell JR, etal., J Biol Chem. 2016 Jan 22;291(4):1948-56. doi: 10.1074/jbc.M115.705319. Epub 2015 Dec 1.
RGD ID: 11532172
Pubmed: PMID:26627835   (View Abstract at PubMed)
PMCID: PMC4722470   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M115.705319   (Journal Full-text)

Variation in PPP3CC, the gene that encodes the gamma isoform of the calcineurin catalytic subunit, has been reported to be associated with schizophrenia. Because of its low expression level in most tissues, there has been little research devoted to the specific function of the calcineurin Agamma (CNAgamma) versus the calcineurin Aalpha (CNAalpha) and calcineurin Abeta (CNAbeta) catalytic isoforms. Consequently, we have a limited understanding of the role of altered CNAgamma function in psychiatric disease. In this study, we demonstrate that CNAgamma is present in the rodent and human brain and dephosphorylates a presynaptic substrate of calcineurin. Through a combination of immunocytochemistry and immuno-EM, we further show that CNAgamma is localized to presynaptic terminals in hippocampal neurons. Critically, we demonstrate that RNAi-mediated knockdown of CNAgamma leads to a disruption of synaptic vesicle cycling in cultured rat hippocampal neurons. These data indicate that CNAgamma regulates a critical aspect of synaptic vesicle cycling and suggest that variation in PPP3CC may contribute to psychiatric disease by altering presynaptic function.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glutamatergic synapse is_active_inIDA 11532172PMID:26627835SynGO 
glutamatergic synapse is_active_inIMP 11532172PMID:26627835SynGO 
presynapse  IDA 11532172 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppp3cc  (protein phosphatase 3 catalytic subunit gamma)

Objects referenced in this article
Gene Ppp3cb protein phosphatase 3 catalytic subunit beta Rattus norvegicus

Additional Information