title: 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.
authors: Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, Toronto, ON, Canada M5G 1X8.
authors: Evgueni A
authors: EA
authors: Ivakine
authors: Brooke A
authors: BA
authors: Acton
authors: Vivek
authors: V
authors: Mahadevan
authors: Jake
authors: J
authors: Ormond
authors: Man
authors: M
authors: Tang
authors: Jessica C
authors: JC
authors: Pressey
authors: Michelle Y
authors: MY
authors: Huang
authors: David
authors: D
authors: Ng
authors: Eric
authors: E
authors: Delpire
authors: Michael W
authors: MW
authors: Salter
authors: Melanie A
authors: MA
authors: Woodin
authors: Roderick R
authors: RR
authors: McInnes
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology*; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D027981:Symporters / Q000737:chemistry / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D002712:Chlorides; D008565:Membrane Proteins; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C539204:NETO2 protein, mouse
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