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Medientyp:
E-Artikel
Titel:
Dynamic NHERF interaction with TRPC4/5 proteins is required for channel gating by diacylglycerol
Beteiligte:
Storch, Ursula;
Forst, Anna-Lena;
Pardatscher, Franziska;
Erdogmus, Serap;
Philipp, Maximilian;
Gregoritza, Manuel;
Mederos y Schnitzler, Michael;
Gudermann, Thomas
Erschienen:
Proceedings of the National Academy of Sciences, 2017
Erschienen in:Proceedings of the National Academy of Sciences
Sprache:
Englisch
DOI:
10.1073/pnas.1612263114
ISSN:
0027-8424;
1091-6490
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Significance</jats:title>
<jats:p>
Transient receptor potential cation (TRPC) 4 and 5 channels are nonselective cation channels activated via G protein-coupled receptors. In contrast to all other TRPC channels, they are regarded as insensitive to the phospholipase C (PLC) product diacylglycerol (DAG). Deeper insight into the G protein-dependent activation mechanism of TRPC4/5 channels is lacking. In this study we unravel the G
<jats:sub>q/11</jats:sub>
protein-mediated signaling pathway leading to TRPC4/5 activation. Depletion of phosphatidylinositol 4,5-bisphosphate causes a conformational change of the TRPC5 C terminus leading to dissociation of Na
<jats:sup>+</jats:sup>
/H
<jats:sup>+</jats:sup>
exchanger regulatory factor (NHERF) proteins thereby inducing a DAG-sensitive channel state. Our findings reveal a previously unidentified activation mechanism of TRPC4/5 channels with NHERF proteins as dynamic regulators of channel activity. Moreover, we demonstrate that TRPC channels are DAG sensitive.
</jats:p>