Huber, Tobias B. and Schermer, Bernhard and Mueller, Roman Ulrich and Hoehne, Martin and Bartram, Malte and Calixto, Andrea and Hagmann, Henning and Reinhardt, Christian and Koos, Fabienne and Kunzelmann, Karl and Shirokova, Elena and Krautwurst, Dietmar and Harteneck, Christian and Simons, Matias and Pavenstaedt, Hermann and Kerjaschki, Dontscho and Thiele, Christoph and Walz, Gerd and Chalfie, Martin and Benzing, Thomas (2006) Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 103 (46). pp. 17079-17086. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
The prohibitin (PHB)-domain proteins are membrane proteins that regulate a variety of biological activities, including mechanosensation, osmotic homeostasis, and cell signaling, although the mechanism of this regulation is unknown. We have studied two members of this large protein family, MEC-2, which is needed for touch sensitivity in Caenorhabditis elegans, and Poclocin, a protein involved in the function of the filtration barrier in the mammalian kidney, and find that both proteins bind cholesterol. This binding requires the PHB domain (including palmitoylation sites within it) and part of the N-terminally adjacent hydrophobic domain that attaches the proteins to the inner leaflet of the plasma membrane. By binding to MEC-2 and Poclocin, cholesterol associates with ion-channel complexes to which these proteins bind: DEG/ENaC channels for MEC-2 and TRPC channels for Poclocin. Both the MEC-2-dependent activation of mechanosensation and the Podocin-depen dent activation of TRPC channels require cholesterol. Thus, MEC-2, Poclocin, and probably many, other PHB-domain proteins by binding to themselves, cholesterol, and target proteins regulate the formation and function of large protein-cholesterol supercomplexes in the plasma membrane.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONGENITAL NEPHROTIC SYNDROME; TOUCH RECEPTOR NEURONS; C-ELEGANS; SLIT DIAPHRAGM; GLOMERULAR PROTEIN; STOMATIN; DOMAIN; IDENTIFICATION; NEPHRIN; TRPC6; prohibitin-domain proteins; TRP channels; DEG/ENaC channels; slit diaphragm; mechanosensation |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Jan 2021 09:26 |
| Last Modified: | 19 Jan 2021 09:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33774 |
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