Physics of Living Systems (PoLS) Seminar - Dr. Shashank Shekhar
Speaker: Dr. Shashank Shekhar, Emory University.
Host: Prof. Peter Yunker
Title: : Barbed end depolymerization and pointed end polymerization - turning treadmilling on its head
Actin is an essential protein. For over two decades, intracellular actin filaments have been thought to elongate at their barbed ends and depolymerize from pointed ends. This process, referred to as “treadmilling” has formed the central bedrock of our understanding of actin dynamics. Recent results from our lab however suggest that the treadmilling dogma might not always hold true. Using a combination of in vitro multicolor single molecule and single filament reconstitution experiments, we have discovered two new activities that call for reevaluation of the treadmilling dogma. First, we discovered the first-ever pointed-end polymerase VopF that processively polymerizes filament pointed ends in cells and from purified proteins. Further, VopF accelerates polymerization in presence of profilin and is a mechanosensitive protein - its rate of polymerization increases under pN-range pulling forces. Second, we have recently discovered that twinfilin, a member of the cofilin family of proteins, induces depolymerization of filament barbed ends. Interestingly we find that the depolymerase twinfilin, polymerase formin and blocker CP form a multicomponent complex at the filament barbed end. Importantly, both of these processes persist in physiological conditions containing high concentrations of profilin-bound monomers – strongly indicating intracellular implications for these newly discovered activities. Taken together, our findings call for taking a fresh look at actin treadmilling and its implications in cellular actin dynamics.
Dr. Shashank Shekhar is an assistant professor of physics and cell biology at Emory University. His research interests in biological self-assembly lie at the interface of physics, biology and biochemistry. He is the recipient of several awards including the Whitman Early Career Award at the Marine Biological Laboratory and the Grand advances in Biology Prize from the French Academy of Sciences. He received his PhD in experimental cell biophysics from University of Twente (The Netherlands). He earned his master’s in Nanoscience and Molecular Bioengineering from TU Delft (Netherlands) and TU Dresden (Germany) and undergraduate degree in Physics in India.