Such muscle cell fusion, the researchers say, is not only important for understanding normal muscle growth, but also muscle regeneration after injury or disease. The work, they believe, could further development of therapies for muscular dystrophy or age-related muscle wasting.
Their report on muscle cell cytoskeletons, published in Developmental Cell May 17, adds detail to a previous study last year showing that actin — a main building block of the cell’s cytoskeleton — is required to form those finger-like projections and stimulate muscle cell merges. The new discovery outlines the intricate dance required among cytoskeleton-regulating proteins to precisely construct protrusions that promote muscle cell merging. Specifically, the Johns Hopkins team uncovered the activity of a regulatory protein known as “Blown Fuse,” aptly named because muscle cells lacking this protein fail to fuse.
“Blown Fuse was found to play a role in muscle cell fusion 14 years ago,” says Elizabeth Chen, Ph.D. assistant professor of molecular biology and genetics, “and now we know how Blown Fuse regulates the dynamics of the cytoskeleton to facilitate the invasion of one muscle cell by another.”
The test began with researchers putting fluorescent actin in fruit fly muscle cells that incorporated themselves into the growing actin branches in the finger-like protrusions. Then, the researchers used a laser beam to bleach the fluorescent actin in the region of the finger-like protrusions and waited to see whether and how long it would take for new, unbleached actin to spread from other parts of the cell and be taken up by the growing branches in the “fingers.” In normal muscle cells, it took about two minutes for the fluorescence to return. In muscle cells that lacked Blown Fuse, the fluorescence never fully recovered and the cytoskeleton failed to project finger-like protrusions, probably because the WASP-WIP complex does not come off the ends of the actin filaments to start new actin branches.
“These results suggest that the growing ends of the actin cytoskeleton are occupied by the WASP-WIP protein duo and that without Blown Fuse to dissociate with the WASP-WIP complex and push WASP off the ends, new actin branches cannot be started,” says Chen. “And these shorter and stiffer new branches are critical for generating the finger-like membrane protrusions.”
Through a microscope, the Hopkins team compared the finger-like projections from normal cells with cells lacking Blown Fuse. Normal muscle cells form pointy finger-like protrusions that push into the other muscle cell, but cells without Blown Fuse have fewer and floppier protrusions that don’t push their way in to other muscle cells.
“Modulating the stability of the WASP-WIP complex may represent a general mechanism in regulating cytoskeleton dynamics and generating membrane protrusions,” says Chen.
The study was funded by grants from the National Institutes of Health, the American Heart Association and the Muscular Dystrophy Association.
Other authors of the report are Peng Jin, Rui Duan, Fengbao Luo and Sabrina Hong of the Johns Hopkins University School of Medicine and Guofeng Zhang of the National Institute of Biomedical Imaging and Bioengineering.
Vanessa McMains | EurekAlert!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy