PXD006046

PXD006046 is an original dataset announced via ProteomeXchange.

Title	KCC2 Proteome
Description	KCC2 is a neuron-specific K+-Cl‑ cotransporter essential for establishing the Cl- gradient required for hyperpolarizing inhibition. KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to numerous human neurological disorders including epilepsy and neuropathic pain. Using unbiased functional proteomics, we identified the KCC2-interactome with the goal of determining KCC2-protein interactions that regulate KCC2 function. Our analysis revealed that KCC2 interacts with a diverse set of proteins, and its most predominant interactors play important roles in postsynaptic receptor recycling. The most abundant KCC2 interactor is a neuronal endocytic regulatory protein termed PACSIN1 (SYNDAPIN1). We verified the PACSIN1-KCC2 interaction biochemically and demonstrated that shRNA knockdown of PACSIN1 in hippocampal neurons significantly increases KCC2 expression and hyperpolarizes the reversal potential for Cl-. Overall, our global native-KCC2 interactome and subsequent characterization revealed PACSIN1 as a novel and potent negative regulator of KCC2.
HostingRepository	PRIDE
AnnounceDate	2017-10-16
AnnouncementXML	Submission_2017-11-06_06:31:04.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vivek Mahadevan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	(R)-5-oxo-1: 4-tetrahydrothiazine-3-carboxylic acid; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-07 08:20:41	ID requested
1	2017-10-16 09:01:56	announced
⏵ 2	2017-11-06 06:31:05	announced	Updated publication reference for PubMed record(s): 29028184.

Mahadevan V, Khademullah CS, Dargaei Z, Chevrier J, Uvarov P, Kwan J, Bagshaw RD, Pawson T, Emili A, De Koninck Y, Anggono V, Airaksinen M, Woodin MA, Native KCC2 interactome reveals PACSIN1 as a critical regulator of synaptic inhibition. Elife, 6():(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Neuronal Chloride homeostasis, Cation chloride cotransporter, KCC2, SLC12A5, LC/MS, Proteomics, Interacting proteins, GABA, Glutamate, E/I balance

Melanie Woodin
contact affiliation	Associate Professor, Department of Cell and Systems Biology Director, Human Biology Program University of Toronto, Canada
contact email	m.woodin@utoronto.ca
lab head
Vivek Mahadevan
contact affiliation	University of Toronto
contact email	vivek.mahadevan@mail.utoronto.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD006046

PRIDE project URI

• PRIDE
  1. PXD006046
     1. Label: PRIDE project
     2. Name: KCC2 Proteome