Roberto Dominguez, PhD, William Maul Measey Presidential Professor of Physiology, Perelman School of Medicine, University of Pennsylvania

Speaker: 

Roberto Dominguez, PhD

William Maul Measey Presidential Professor of Physiology

Perelman School of Medicine

University of Pennsylvania

Title: Cryo-EM Reveals Mechanisms of Elongation and Depolymerization at Actin Filament
Ends

Abstract: 

The barbed end of actin filaments is typically oriented toward cellular membranes, including those of cells, organelles, and pathogens. As filaments grow, they exert force on these membranes, driving essential processes such as cell motility, organelle trafficking, cytokinesis, and the establishment of cell polarity. To sustain continuous growth, filaments must also depolymerize from the opposite, pointed end to replenish the monomer pool. In cells, both barbed-end elongation and pointed-end depolymerization occur significantly faster than in vitro, due to the action of numerous proteins that accelerate these processes. The primary families of barbed-end elongators are Formins and Ena/VASP, which act synergistically with Profilin to promote filament growth. Similarly, ADF/Cofilin, in partnership with Cyclase-Associated Protein (CAP), enhances pointed-end depolymerization. Severing proteins—including ADF/Cofilin (again working synergistically with CAP) and Gelsolin—contribute to both elongation and depolymerization by breaking filaments and generating new barbed and pointed ends that can in turn undergo rapid growth or shrinkage. Finally, end-capping proteins such as CP (also known as CapZ) and Tropomodulin bind to barbed and pointed ends, respectively, to prevent monomer addition or dissociation. The structural and functional mechanisms underlying these processes are only beginning to emerge, thanks in large part to work from our lab using cryo-electron microscopy (cryo-EM) and biochemistry. I will present several cryo-EM structures that provide atomic snapshots of the multi-step mechanisms that mediate elongation, depolymerization, severing, and capping to control actin filament dynamics in cells.

Bio: 

TBD