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

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.

SUBMITTER: Ivakine EA

PROVIDER: S-EPMC3587235 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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

Ivakine Evgueni A EA Acton Brooke A BA Mahadevan Vivek V Ormond Jake J Tang Man M Pressey Jessica C JC Huang Michelle Y MY Ng David D Delpire Eric E Salter Michael W MW Woodin Melanie A MA McInnes Roderick R RR

Proceedings of the National Academy of Sciences of the United States of America 20130211 9

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 f ...[more]

PMID: 23401525

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