Sunday driver gene headed the wrong way in inherited muscle diseases

March 26, 2014

Skeletal muscle cells with unevenly spaced nuclei, or nuclei in the wrong location, are telltale signs of such inherited muscle diseases as Emery-Dreifuss muscular dystrophy, which occurs in one out of every 100,000 births, and centronuclear myopathy, which affects one out of every 50,000 infants.

What goes wrong during myogenesis, the formation and maintenance of , to produce these inherited muscle diseases?

Research using the fruit fly Drosophila melanogaster has implicated the gene known as Sunday Driver (Syd) as a novel regulator of myogenesis. The fruit fly studies showed that Syd encodes a protein, the transport adapter Syd, which interacts with cortical factors that enable the motor protein Dynein to pull muscle nuclei into place.

The scientists, who are based at Weill Cornell Graduate School of Medical Sciences and the Sloan Kettering Institute of Memorial Sloan-Kettering Cancer Center, both in New York City, mutated the Syd gene in embryonic and larval muscles of the fruit fly. As a result, the nuclei in the fly's were unevenly spaced and clustered.

The scientists also determined that JNK (c-Jun N-terminal kinase) signaling was essential for correct intracellular organization. In the absence of JNK signaling, Syd and Dynein proteins were restricted to the space surrounding the cell nucleus. While overactive JNK signaling allowed the correct transport of Syd and Dynein to the cell cortex at the muscle ends, it prevented their downstream functions that work to pull muscle nuclei into proper position. These defects could be rescued by expression of JIP3 (JNK Interacting Protein 3), the mammalian homolog of Drosophila Syd, suggesting that these cellular activities are conserved from flies to humans and highlighting the utility of Drosophila as a model organism to elucidate key features of human disease.

Most important, during locomotion assays, the larvae with defective Syd protein and abnormally positioned nuclei were weak crawlers, mimicking disease states in humans. While muscle-specific depletion of Syd reduced muscle output, locomotion was rescued by expression of mammalian JIP3, suggesting that muscle cell nuclear position and muscle force generation are functionally linked in .

Explore further: New discovery of proteins involved in positioning muscular nuclei

More information: Abstract: "Sunday Driver (Syd/JIP3) and JNK Signaling are Required for Myogenesis and Muscle Function." Victoria K. Schulman1,2, Eric S. Folker2, Mary K. Baylies1,2. 1) Weill Cornell Graduate School of Medical Sciences, New York, NY; 2) Sloan-Kettering Institute, New York, NY.

Related Stories

Breast cancer gene protects against obesity, diabetes

March 12, 2014

(Medical Xpress)—The gene known to be associated with breast cancer susceptibility, BRCA 1, plays a critical role in the normal metabolic function of skeletal muscle, according to a new study led by University of Maryland ...

Tension triggers muscle building

March 14, 2014

Skeletal muscles are built from small contractile units, the sarcomeres. Many of these sarcomeres are connected in a well-ordered series to form myofibrils that span from one muscle end to the other. Contractions of these ...

Recommended for you

New class of RNA tumor suppressors identified

November 23, 2015

A pair of RNA molecules originally thought to be no more than cellular housekeepers are deleted in over a quarter of common human cancers, according to researchers at the Stanford University School of Medicine. Breast cancer ...

Batten disease may benefit from gene therapy

November 11, 2015

In a study of dogs, scientists showed that a new way to deliver replacement genes may be effective at slowing the development of childhood Batten disease, a rare and fatal neurological disorder. The key may be to inject viruses ...

Molecular clocks control mutation rate in human cells

November 9, 2015

Every cell in the human body contains a copy of the human genome. Through the course of a lifetime all cells are thought to acquire mutations in their genomes. Some of the mutational processes generating these mutations do ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.