How are ion pumps and agrin signaling integrated?
Na(+),K(+)-ATPase (NKA) has a fundamental role in ion transport across the plasma membrane of animal cells and uses approximately 50% of brain energy consumption. Recent work has uncovered additional roles for NKA in signal transduction. How might such different functions of the sodium-potassium pump be connected and regulated? We envision an integrated model of ion pumping and signaling, considering in particular the recently discovered regulation of the sodium-potassium pump by agrin, a protein that is cleaved specifically by neurotrypsin at the synapse. Based on the recently solved structure of NKA and sequence analysis, we propose a molecular model for the agrin-NKA interaction, in which agrin displaces the NKA β-subunit and exploits the ouabain-binding pocket.
Tidow
Henning
H
Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Denmark. tidow@bioxray.au.dk
Aperia
Anita
A
Nissen
Poul
P
D018171:Agrin / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D008958:Models, Molecular; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
D018171:Agrin; D000254:Sodium-Potassium-Exchanging ATPase