Sunday driver gene headed the wrong way in inherited muscle diseases

March 26, 2014, Genetics Society of America

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: Nuclei in wrong place may be cause, not result, of inherited muscle diseases

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. abstracts.genetics-gsa.org/cgi … il.pl?absno=14531108

Related Stories

Nuclei in wrong place may be cause, not result, of inherited muscle diseases

December 16, 2013
Incorrectly positioned nuclei are not merely a sign but a possible cause of human congenital myopathies, a string of inherited muscle diseases, Victoria Schulman, graduate student at Weill Cornell Graduate School of Medical ...

Promoting muscle regeneration in a mouse model of muscular dystrophy

April 1, 2013
Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease caused by mutations in the protein dystrophin. Dystrophin functions to protect muscle cells from injury and loss of functional dystrophin results ...

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 ...

New discovery of proteins involved in positioning muscular nuclei

March 20, 2012
The position of cellular nuclei in muscle fibres has an important role in some muscle weaknesses. Edgar Gomes, an Inserm researcher in the myology group at the Institute of Myology (mixed Inserm/UPMC unit) recently made this ...

Cell discovery could hold key to causes of inherited diseases

February 26, 2013
Fresh insights into the protective seal that surrounds the DNA of our cells could help develop treatments for inherited muscle, brain, bone and skin disorders.

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 ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

0 comments

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.