Na(+)-H(+) exchange in salivary secretory cells is controlled by an intracellular Na(+) receptor.
It recently has been shown that epithelial Na(+) channels are controlled by a receptor for intracellular Na(+), a G protein (G(o)), and a ubiquitin-protein ligase (Nedd4). Furthermore, mutations in the epithelial Na(+) channel that underlie the autosomal dominant form of hypertension known as Liddle's syndrome inhibit feedback control of Na(+) channels by intracellular Na(+). Because all epithelia, including those such as secretory epithelia, which do not express Na(+) channels, need to maintain a stable cytosolic Na(+) concentration ([Na(+)](i)) despite fluctuating rates of transepithelial Na(+) transport, these discoveries raise the question of whether other Na(+) transporting systems in epithelia also may be regulated by this feedback pathway. Here we show in mouse mandibular secretory (endpiece) cells that the Na(+)-H(+) exchanger, NHE1, which provides a major pathway for Na(+) transport in salivary secretory cells, is inhibited by raised [Na(+)](i) acting via a Na(+) receptor and G(o). This inhibition involves ubiquitination, but does not involve the ubiquitin protein ligase, Nedd4. We conclude that control of membrane transport systems by intracellular Na(+) receptors may provide a general mechanism for regulating intracellular Na(+) concentration.
Ishibashi
H
H
Department of Physiology, University of Sydney, Sydney NSW 2006, Australia.
Dinudom
A
A
Harvey
K F
KF
Kumar
S
S
Young
J A
JA
Cook
D I
DI
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D005246:Feedback; D019204:GTP-Binding Proteins; D006863:Hydrogen-Ion Concentration; D008025:Ligases; D008297:Male; D051379:Mice; D000075702:Nedd4 Ubiquitin Protein Ligases; D018408:Patch-Clamp Techniques; D012469:Salivary Glands / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism
D002135:Calcium-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D017923:Sodium-Hydrogen Exchangers; D014452:Ubiquitins; C069139:growth factor-activatable Na-H exchanger NHE-1; D012964:Sodium; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases; D019204:GTP-Binding Proteins; D008025:Ligases