@article {Line201800118, author = {Amy W Lin and Kalbinder K Gill and Marisol Sampedro Casta{\~n}eda and Irene Matucci and Noreen Eder and Suzanne Claxton and Helen Flynn and Ambrosius P Snijders and Roger George and Sila K Ultanir}, title = {Chemical genetic identification of GAK substrates reveals its role in regulating Na+/K+-ATPase}, volume = {1}, number = {6}, elocation-id = {e201800118}, year = {2018}, doi = {10.26508/lsa.201800118}, publisher = {Life Science Alliance}, abstract = {Cyclin G{\textendash}associated kinase (GAK) is a ubiquitous serine/threonine kinase that facilitates clathrin uncoating during vesicle trafficking. GAK phosphorylates a coat adaptor component, AP2M1, to help achieve this function. GAK is also implicated in Parkinson{\textquoteright}s disease through genome-wide association studies. However, GAK{\textquoteright}s role in mammalian neurons remains unclear, and insight may come from identification of further substrates. Employing a chemical genetics method, we show here that the sodium potassium pump (Na+/K+-ATPase) α-subunit Atp1a3 is a GAK target and that GAK regulates Na+/K+-ATPase trafficking to the plasma membrane. Whole-cell patch clamp recordings from CA1 pyramidal neurons in GAK conditional knockout mice show a larger change in resting membrane potential when exposed to the Na+/K+-ATPase blocker ouabain, indicating compromised Na+/K+-ATPase function in GAK knockouts. Our results suggest a modulatory role for GAK via phosphoregulation of substrates such as Atp1a3 during cargo trafficking.}, URL = {https://www.life-science-alliance.org/content/1/6/e201800118}, eprint = {https://www.life-science-alliance.org/content/1/6/e201800118.full.pdf}, journal = {Life Science Alliance} }