Key Culprit Causing Muscle Atrophy Identified To find out, Adams and his colleagues conducted a series of experiments to discover the critical ATF4NAME _______________ Date _______Per#___ target genes. The tests showed that ATF4 caused muscle atrophy by activating the Gadd45a gene.UI researchers have identified a key protein involved Further tests showed Gadd45a didnt need its proteinin muscle atrophy. The protein, Gadd45a, benefactor to do its atrophy work either, meaning itreprograms hundreds of genes inside a muscle cells could act independently of the ATF4 pathway.nucleus, causing the nucleus to dramatically changefrom a cigar shape (top) to a swollen bulb (bottom). "Basically, when we did the experiments, thousands(Credit: Images courtesy of Christopher Adams lab, of mRNAs (the genetic messengers) were measured,University of Iowa.) but only one jumped out, and it was Gadd45a," says Adams, also a faculty scholar at the Fraternal OrderScienceDaily (Aug. 13, 2012) — Whether youre old, of Eagles Diabetes Research Center at the UI. "It washave been ill, or suffered an injury, youve watched the only one that met all the tests criteria."gloomily as your muscles have atrophied. Thedeterioration of muscle -- even slight or gradual -- is The researchers learned that Gadd45a affectedabout as common to the human condition as muscles in two main ways: it instructed muscle cellsbreathing. to produce fewer proteins (needed to maintain muscle), and it caused proteins already existing inYet despite its everyday nature, scientists know little muscle fibers to break down. The result on bothabout what causes skeletal muscles to atrophy. They counts: muscle atrophy.know proteins are responsible, but there arethousands of possible suspects, and parsing the key The team then turned to find out how Gadd45a did itsactors from the poseurs is tricky. In a new paper, work. The nucleus of a muscle cell that is stressedresearchers from the University of Iowa report major changes from a cigar shape to a swollen bulb, withprogress. The team has identified a single protein, enlarged nucleoli (protein containers inside thecalled Gadd45a, and determined that it orchestrates nucleus). When Adams and his team injected40 percent of the gene activity that ultimately causes Gadd45a into a muscle cell, the nucleus changedskeletal muscle to atrophy. Moreover, the researchers shape the same way as if it were stressed.have learned that Gadd45a does its devilish workinside the muscle cells nucleus, causing such a "To put this all together, it means Gadd45a is goingruckus as it reprograms hundreds of genes that it into the muscle nucleus, and it totally changes it, sochanges the nucleuss shape. much so that the changes are visible," Adams said. "Its turning genes on, and its turning genes off. Its"We now understand a key molecular mechanism of changed the cell."skeletal muscle atrophy," says Christopher Adams,associate professor of internal medicine at the UI and Gadd45a changes roughly 600 genes associated withcorresponding author on the paper published in the muscle atrophy, by increasing mRNAs charged eitherJournal of Biological Chemistry. "This finding could with breaking down muscle proteins or reducinghelp us find a therapy for treating muscle atrophy in muscle protein growth. The total is about 40 percentpatients, and we now know a great place to start is by of all mRNAs believed to be involved in musclereducing Gadd45a." deterioration in humans, the researchers reported in the paper.Adams and his team zeroed in on Gadd45a likesleuths following a trail of clues. The researchers "Gadd45a is like a central switch for muscleknew from previous work that when skeletal muscle atrophy," Adams says. "If you can block it, you canis stressed from malnutrition, nerve damage, or conceivably stunt muscle atrophy to a large extent."inactivity, it increases its production of a proteincalled ATF4. That protein, in turn, initiates muscle Review Questions – Write a Summary containing:atrophy by activating a slew of genes. But the detailsremained elusive. For example, are all the genes 1. What is the main idea of the article?equally important or do some play larger roles thanothers? 2. What information presented in the article supports the main idea?