The small GTPase Rem is a potent negative regulator of high voltage-activated Ca2+ channels and a known interacting partner for Ca2+ channel accessory β subunits. The mechanism for Rem-mediated channel inhibition remains controversial, although it has been proposed that CaVβ association is required. Previous work has shown that a C-terminal truncation of Rem (Rem-(1-265)) displays reduced in vivo binding to membrane-localized β2a and lacks channel regulatory function. In this paper, we describe a role for the Rem C terminus in plasma membrane localization through association with phosphatidylinositol lipids. Moreover, Rem-(1-265) can associate with β2a in vitro and β1b in vivo, suggesting that the C terminus does not directly participate in Ca Vβ association. Despite demonstrated β1b binding, Rem-(1-265) was not capable of regulating a CaV1.2-β1b channel complex, indicating that β subunit binding is not sufficient for channel regulation. However, fusion of the CAAX domain from K-Ras4B or H-Ras to the Rem-(1-265) C terminus restored membrane localization and Ca2+ channel regulation, suggesting that β binding and membrane localization are independent events required for channel inhibition.
|Number of pages||10|
|Journal||Journal of Biological Chemistry|
|State||Published - Sep 28 2007|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology