PXD011319

PXD011319 is an original dataset announced via ProteomeXchange.

Title	Chemical Genetic Identification of Cyclin-G-associated kinase (GAK) Substrates Reveals its Role in Regulating Na+/K+-ATPase and Sipa1L1 in Neurons
Description	Recent genetic evidence implicates the serine/threonine kinase cyclin G-associated kinase (GAK) as a Parkinson’s disease risk. However, its role in neuronal function and many downstream effectors remain unclear. Employing a chemical genetics method, we show here that the sodium potassium pump (Na+/K+-ATPase) is a GAK target in the brain. We further show that GAK modulates Na+/K+-ATPase at a novel site affecting both pump localization and function. Whole-cell patch clamp recordings from CA1 pyramidal cells in GAK conditional knockout mice show a larger change in resting membrane potential when exposed to the Na+/K+-ATPase blocker, ouabain, indicating altered Na+/K+-ATPase function in GAK knockouts. Additionally, we show that GAK-deficient neurons have enlarged dendritic spines and we identify the spine associated protein Sipa1L1 (or SPAR) as a GAK target, which may contribute to this effect. Our results reveal novel functions of GAK in neurons.
HostingRepository	PRIDE
AnnounceDate	2019-01-07
AnnouncementXML	Submission_2019-01-14_04:40:17.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Noreen Eder
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-09 07:56:04	ID requested
1	2019-01-07 05:11:50	announced
⏵ 2	2019-01-14 04:40:18	announced	Updated publication reference for PubMed record(s): 30623173.

Lin AW, Gill KK, Casta, ñ, eda MS, Matucci I, Eder N, Claxton S, Flynn H, Snijders AP, George R, Ultanir SK, -ATPase. Life Sci Alliance, 1(6):e201800118(2018) [pubmed]

curator keyword: Biological

submitter keyword: Atp1a3, Cyclin-G-associated kinase, GAK, sodium potassium pump

Sila Ultanir
contact affiliation	Kinases and Brain Development Lab, The Francis Crick Institute (UK)
contact email	sila.ultanir@crick.ac.uk
lab head
Noreen Eder
contact affiliation	The Francis Crick Institute
contact email	noreen.eder@crick.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011319
     1. Label: PRIDE project
     2. Name: Chemical Genetic Identification of Cyclin-G-associated kinase (GAK) Substrates Reveals its Role in Regulating Na+/K+-ATPase and Sipa1L1 in Neurons