Department of Anesthesiology

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

TitleCalcineurin Aγ is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis.
Publication TypeJournal Article
Year of Publication2016
AuthorsCottrell JR, Li B, Kyung JWon, Ashford CJ, Mann JJ, Horvath TL, Ryan TA, Kim SHyun, Gerber DJ
JournalJ Biol Chem
Volume291
Issue4
Pagination1948-56
Date Published2016 Jan 22
ISSN1083-351X
Abstract

Variation in PPP3CC, the gene that encodes the γ 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 Aγ (CNAγ) versus the calcineurin Aα (CNAα) and calcineurin Aβ (CNAβ) catalytic isoforms. Consequently, we have a limited understanding of the role of altered CNAγ function in psychiatric disease. In this study, we demonstrate that CNAγ 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 CNAγ is localized to presynaptic terminals in hippocampal neurons. Critically, we demonstrate that RNAi-mediated knockdown of CNAγ leads to a disruption of synaptic vesicle cycling in cultured rat hippocampal neurons. These data indicate that CNAγ regulates a critical aspect of synaptic vesicle cycling and suggest that variation in PPP3CC may contribute to psychiatric disease by altering presynaptic function.

DOI10.1074/jbc.M115.705319
Alternate JournalJ. Biol. Chem.
PubMed ID26627835
PubMed Central IDPMC4722470