Pressure Modulation of Ras鈥揗embrane Interactions and Intervesicle Transfer
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- 作者：Shobhna Kapoor ; Alexander Werkm眉ller ; Roger S. Goody ; Herbert Waldmann ; Roland Winter
- 刊名：The Journal of the American Chemical Society
- 出版年：2013
- 出版时间：April 24, 2013
- 年：2013
- 卷：135
- 期：16
- 页码：6149-6156
- 全文大小：416K
- 年卷期：v.135,no.16(April 24, 2013)
- ISSN：1520-5126
文摘
Proteins attached to the plasma membrane frequently encounter mechanical stresses, including high hydrostatic pressure (HHP) stress. Signaling pathways involving membrane-associated small GTPases (e.g., Ras) have been identified as critical loci for pressure perturbation. However, the impact of mechanical stimuli on biological outputs is still largely terra incognita. The present study explores the effect of HHP on the membrane association, dissociation, and intervesicle transfer process of N-Ras by using a FRET-based assay to obtain the kinetic parameters and volumetric properties along the reaction path of these processes. Notably, membrane association is fostered upon pressurization. Conversely, depending on the nature and lateral organization of the lipid membrane, acceleration or retardation is observed for the dissociation step. In addition, HHP can be inferred as a positive regulator of N-Ras clustering, in particular in heterogeneous membranes. The susceptibility of membrane interaction to pressure raises the idea of a role of lipidated signaling molecules as mechanosensors, transducing mechanical stimuli to chemical signals by regulating their membrane binding and dissociation. Finally, our results provide first insights into the influence of pressure on membrane-associated Ras-controlled signaling events in organisms living under extreme environmental conditions such as those that are encountered in the deep sea and sub-seafloor environments, where pressures reach the kilobar (100 MPa) range.