Dr. Nicanor Gonzalez-Morales
Biology Department, McGill University
Monday, March 9 10:30am – 11:30am Miller Hall 201
Muscles are made up of muscle fibers, each containing thousands of cylindrical segments called sarcomeres, which are the smallest contractile unit of muscles. When animals move, proteins in the sarcomere move past each other, shortening the muscles. In the relaxed state, all sarcomeres have the same length and diameter. To study muscle biology I use the fruit fly Drosophila. Their flight muscles are extremely regular, because they have to mediate 200 small contractions per second, and are therefore ideally suited to detect phenotypic variations. Sarcomeres are composed of antiparallel actin and myosin filaments that slide past each other. Both filaments are anchored to big protein complexes that provide structural stability. The Z-discs anchor actin filaments and the M-lines myosin filaments. This fascinating structural arrangement provides the basis of muscle contraction. The general sarcomere structure is well known but the mechanisms that assemble sarcomeres from unorganized components and maintain sarcomeres during muscle contractions are not well understood. The Z-disc anchors actin filaments and thus coordinates sarcomere assembly and function. Accordingly, most mutations linked to myopathies are components of the Z-disc.
To study sarcomere assembly and function, I combine the power of Drosophila genetics with quantitative microscopy and a novel bioinformatics method for inferring protein-protein interactions. First, I will talk about how the scaffolding protein Zasp mediates sarcomere growth through a finely tuned protein oligomerization mechanism. Oligomerization is induced by long Zasp isoforms and terminated upon upregulation of shorter Zasp isoforms, which lack multivalent LIM domains. The balance between these two isoforms sets the stereotyped size of sarcomeres. Second, I will describe how elastic proteins help maintain sarcomere stability during muscle contraction. In this model, two elastic proteins filamin and titin function together as an elastic bridge between thin filaments of opposing sarcomeres. Both filamin and titin have protein regions than unfold upon pulling forces and then refold, essentially working as springs. Their function is required for compensating for the contractile forces and maintaining the sarcomere structure. Finally, I will discuss future directions and approaches.