Muscles Need ‘Chaperone’ Proteins,
But More Not Always Better

MDA grantee Henry Epstein at the University of Texas Medical Branch at Galveston and colleagues have found that precise levels of a protein called UNC-45 may be necessary for formation and maintenance of heart and skeletal muscles.

In an April 23 cover story in the Journal of Cell Biology, the investigators describe how either a shortage or an excess of UNC-45 interferes with the assembly of a key muscle protein, myosin. Myosin and actin, which form so-called thick and thin muscle filaments, are the two principal proteins involved in muscle contraction.

UNC-45 belongs to a class of proteins known as molecular “chaperones,” whose job it is to make sure that newly synthesized proteins fold into their correct shapes; and that if correct folding isn’t possible, to ensure they’re destroyed.

That a deficiency of the UNC-45 chaperone disrupted myosin formation and caused muscle paralysis in worms was already known. But the new study shows that, surprisingly, too much of it also results in partial paralysis, at least in the laboratory worms. The researchers say they think having too much UNC-45 may trap and dispose of myosin protein molecules before they’ve had a chance to form filaments.

Epstein said he thinks the worm data is likely to be applicable to humans and that precise regulation of UNC-45 in humans may be important to prevent muscle wasting and heart failure.

Dysregulation of this chaperone protein may underlie the type of wasting seen in neuromuscular diseases, cancer, burns, aging and other conditions, he said.