Cowling et al. report how to build muscle mass with FHL1. The protein partners with and activates the transcription factor, NFATc1. Encouraging this partnership might provide a possible treatment for muscle wasting disorders. The article will appear in the December 15, 2008 issue of The Journal of Cell Biology (JCB).
Mutations in FHL1 are present in several myopathies, including reducing-body myopathy (RBM), but until now, both the molecular mechanisms causing the disease, and the regular function of FHL1 in healthy tissue, remained unknown.
To address this, Cowling et al. overexpressed FHL1 in both transgenic mice and cultured myoblasts. The mice developed skeletal muscle hypertrophy, and showed increased strength and endurance. Overexpression in myoblasts also increased cell fusion, resulting in hypertrophic myotubes. These phenotypes are similar to those caused by the calcineurin/NFAT pathway and, indeed, inhibiting calcineurin blocked the effects of FHL1 overexpression in vitro. The authors showed that FHL1 binds to and enhances the transcriptional activity of NFATc1 in vitro and in vivo.
So what goes wrong when FHL1 is mutated? In RBM, mutant FHL1 accumulates in cytoplasmic aggregates called reducing bodies, probably as a result of misfolding. When these mutants were expressed in cultured myoblasts, they also aggregated, and did not induce hypertrophy. Cowling and colleagues found that NFATc1 was sequestered to the aggregates, and was therefore unable to activate its target genes.
Rita Sullivan | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Materials Sciences
19.07.2018 | Earth Sciences
19.07.2018 | Life Sciences