Deciphering the Mechanisms of Actin Filament Architecture in Striated Muscle

Striated muscle cells contain arrays of protein filaments assembled into contractile units that are nearly crystalline in structure. Since efficient contraction is predicated upon accurate overlap of thin and thick filaments, proper control of filament length is absolutely critical. However, the mechanisms that precisely regulate thin filament length are still largely unknown. Dr. Gregorio's laboratory has recently identified a novel actin regulatory protein, leiomodin 2 (Lmod2) as a regulator of thin filament length. Her laboratory found that Lmod2 is a pointed end actin filament elongation factor (the first identified in any mammalian cell). The goals of Dr. Gregorio's current research are to determine mechanisms by which actin-thin filament architecture is regulated in cardiac muscle, the role Lmod2 plays in this regulation, and how defects in this regulation contribute to cardiomyopathies.