Interdomain Interactions Control Ca2+-Dependent Potentiation in the Cation Channel TRPV4

Several Ca2+-permeable channels, including the non-selective cation channel TRPV4, are subject to Ca2+-dependent facilitation. Although it has been clearly demonstrated in functional experiments that calmodulin (CaM) binding to intracellular domains of TRP channels is involved in this process, the molecular mechanism remains elusive. In this study, we provide experimental evidence for a comprehensive molecular model that explains Ca2+-dependent facilitation of TRPV4. In the resting state, an intracellular domain from the channel N terminus forms an autoinhibitory complex with a C-terminal domain that includes a high-affinity CaM binding site. CaM binding, secondary to rises in intracellular Ca2+, displaces the N-terminal domain which may then form a homologous interaction with an identical domain from a second subunit. This represents a novel potentiation mechanism that may also be relevant in other Ca2+-permeable channels

PACSINs bind to the TRPV4 cation channel. PACSIN 3 modulates the subcellular localization of TRPV4.

Contains fulltext : 51163.pdf (Publisher’s version ) (Open Access)TRPV4 is a cation channel that responds to a variety of stimuli including mechanical forces, temperature, and ligand binding. We set out to identify TRPV4-interacting proteins by performing yeast two-hybrid screens, and we isolated with the avian TRPV4 amino terminus the chicken orthologues of mammalian PACSINs 1 and 3. The PACSINs are a protein family consisting of three members that have been implicated in synaptic vesicular membrane trafficking and regulation of dynamin-mediated endocytotic processes. In biochemical interaction assays we found that all three murine PACSIN isoforms can bind to the amino terminus of rodent TRPV4. No member of the PACSIN protein family was able to biochemically interact with TRPV1 and TRPV2. Co-expression of PACSIN 3, but not PACSINs 1 and 2, shifted the ratio of plasma membrane-associated versus cytosolic TRPV4 toward an apparent increase of plasma membrane-associated TRPV4 protein. A similar shift was also observable when we blocked dynamin-mediated endocytotic processes, suggesting that PACSIN 3 specifically affects the endocytosis of TRPV4, thereby modulating the subcellular localization of the ion channel. Mutational analysis shows that the interaction of the two proteins requires both a TRPV4-specific proline-rich domain upstream of the ankyrin repeats of the channel and the carboxyl-terminal Src homology 3 domain of PACSIN 3. Such a functional interaction could be important in cell types that show distribution of both proteins to the same subcellular regions such as renal tubule cells where the proteins are associated with the luminal plasma membrane

Core-mantle interactions for Mercury

Mercury is the target of two space missions: MESSENGER (NASA) which orbit insertion is planned for March 2011, and ESA/JAXA BepiColombo, that should be launched in 2014. Their instruments will observe the surface of the planet with a high accuracy (about 1 arcsec for BepiColombo), what motivates studying its rotation. Mercury is assumed to be composed of a rigid mantle and an at least partially molten core. We here study the influence of the core-mantle interactions on the rotation perturbed by the solar gravitational interaction, by modeling the core as an ellipsoidal cavity filled with inviscid fluid of constant uniform density and vorticity. We use both analytical (Lie transforms) and numerical tools to study this rotation, with different shapes of the core. We express in particular the proper frequencies of the system, because they characterize the response of Mercury to the different solicitations, due to the orbital motion of Mercury around the Sun. We show that, contrary to its size, the shape of the core cannot be determined from observations of either longitudinal or polar motions. However, we highlight the strong influence of a resonance between the proper frequency of the core and the spin of Mercury that raises the velocity field inside the core. We show that the key parameter is the polar flattening of the core. This effect cannot be directly derived from observations of the surface of Mercury, but we cannot exclude the possibility of an indirect detection by measuring the magnetic field.Comment: MNRAS, in pres