The gamma-subunit of (Na+,K+)-ATPase: A representative example of human single transmembrane protein with a key regulatory role

The (Na+,K+)-ATPase is a plasma membrane protein complex composed of at lea st three subunits (alpha,beta,gamma) that couples the exchange of three cyt oplasmic Naf ions with two extracellular K+ ions, to the hydrolysis of one molecule of ATP in most animal cells. The gamma -subunit is a 66 residue me mbrane protein associated with the active alpha/beta binary complex. It can be considered as an archetype of single transmembrane proteins (type I) wh ich may play a modulatory role upon association with functional membrane pa rtners. This paper highlights similar associations observed with other ATPa ses such as the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA1/SERCA2a), b ut also with Cl- and/or K+ currents, ionic channels (HERG, KCNQ1) and G-pro tein coupled receptors (adrenomedullin, CGRP and calcitonin) which are of p articular interest in the cardiovascular field. Here is reviewed the assess ed or suggested regulatory role of a family of small plasma/SR associated m embrane proteins including gamma -subunit, phospholemman, Mat 8, KCNE (type 1, 2 and 3), RAMP (type 1, 2 and 3), sarcolipin and phospholamban, mainly found in muscular and vascular tissues. These proteins are critical in cont rolling important biological processes which derive from specific associati ons with a binding partner and particular subcellular localizations.