| First Author | Cottrell JR | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 4 | Pages | 1948-56 |
| PubMed ID | 26627835 | Mgi Jnum | J:230043 |
| Mgi Id | MGI:5755317 | Doi | 10.1074/jbc.M115.705319 |
| Citation | Cottrell JR, et al. (2016) Calcineurin Agamma is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis. J Biol Chem 291(4):1948-56 |
| abstractText | 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. |
