Premium
Role for cholesterol and caveolin‐rich membrane microdomains in controlling the activity Na+/H+ exchange 1 independently of mitogenic stimulation
Author(s) -
HUC Laurence Therese,
Tekpli Xavier,
Lacroix Jerome,
Rissel Mary,
Poët Mallorie,
Noel Josette,
DimancheBoitrel Marietherese,
Counillon Laurent,
LagadicGossmann Dominique
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1425
Subject(s) - chemistry , phosphorylation , stimulation , microbiology and biotechnology , transporter , membrane , lipid microdomain , sodium–hydrogen antiporter , allosteric regulation , lipid raft , cholesterol , biochemistry , endocrinology , receptor , biology , sodium , gene , organic chemistry
The Na + /H + exchanger 1 NHE‐1 is a ubiquitous membrane transporter mainly involved in pH and cell volume regulation. NHE‐1 activation by H + is carried out according to the Monod‐Wyman‐Changeux model in which the dimeric NHE‐1 oscillates between a low and a high affinity conformation, the balance of which being defined by the ratio between the two forms L 0 . Influence of cholesterol‐ and caveolin‐rich microdomains on NHE‐1 activity is examined, by using a cholesterol depleting agent, methyl‐β‐cyclodextrin (MBCD). MBCD induce NHE‐1 activation, by modulating its allosteric balance, these effects being reverted by cholesterol repletion. This activation appears to be associated with NHE‐1 relocalization outside caveolin‐rich microdomains and distinct from mitogenic stimulation of NHE‐1, since MBCD and serum cotreatments are additive; besides, serum alone stimulates this transporter without modifying its localization. Finally, MBCD activate a serum‐insensitive mutated NHE‐1 form and this process occurs independently of MAP kinase phosphorylation. In conclusion, the membrane localization of NHE‐1 in or out microdomains seems to be an essentiel regulator of NHE1 activity, independently of mitogenic action.