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National Academy of Sciences, Proceedings of the National Academy of Sciences, 9(110), p. 3561-3566, 2013

DOI: 10.1073/pnas.1212907110

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Neto2 is a KCC2 interacting protein required for neuronal Cl− regulation in hippocampal neurons

Journal article published in 2013 by Evgueni A. Ivakine, Brooke A. Acton, Vivek Mahadevan ORCID, Jake Ormond, Man Tang, Jessica C. Pressey, Michelle Y. Huang, David Ng, Eric Delpire, Michael W. Salter, Melanie A. Woodin, Roderick R. McInnes
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

KCC2 is a neuron-specific K + –Cl − cotransporter that is essential for Cl − homeostasis and fast inhibitory synaptic transmission in the mature CNS. Despite the critical role of KCC2 in neurons, the mechanisms regulating its function are not understood. Here, we show that KCC2 is critically regulated by the single-pass transmembrane protein neuropilin and tolloid like-2 (Neto2). Neto2 is required to maintain the normal abundance of KCC2 and specifically associates with the active oligomeric form of the transporter. Loss of the Neto2:KCC2 interaction reduced KCC2-mediated Cl − extrusion, resulting in decreased synaptic inhibition in hippocampal neurons.