Moriah Beck photoMoriah Beck
Assistant Professor, Chemistry
Wichita State University

Palladin and regulation of actin dynamics

Mentor: John Cooper Professor, Cell Biology and Physiology
Washington University in St. Louis, St. Louis, MO

At least 90 percent of cancer deaths result from metastasis. Therefore it is critical to understand how a population of cells called Palladin differs from normal tumor cells. Considerable evidence suggest that the activities of palladin and the alpha-actinin are coordinately regulated in metastatic cells. In this project Beck will focus on the interaction between palladin and alpha-actinin in coordinately regulating actin dynamics to test the hypothesis that this complex is critical for the motility and invasion properties necessary to the migration of cancer.

Palladin is a novel protein that is highly conserved among vertebrate species and is a key regulator of actin organization within migrating cells. Current evidence suggests that palladin occupies an unusual functional niche as it functions as both an actin-crosslinking protein and a molecular scaffold that binds several other actin-regulating proteins. Palladin appears to be involved in both normal cell migration and invasive cell motility, yet its precise molecular role in organizing the actin cytoskeleton is unknown. In cell-based assays, the direct role of a particular protein or complex in cytoskeletal dynamics and cell motility can be difficult to resolve due to the intricate network of proteins involved. In this research, Beck will determine how palladin and its binding partners influence actin filament assembly and its disassembly using biochemical approaches. The proposed studies will address the mechanistic gaps in knowledge about how palladin, both directly and in complex, affects actin dynamics; and provide a greater understanding of palladin's role in cancer metastasis.

Preliminary experiments indicate that palladin decreases de novo actin filament nucleation by Arp2/3 complex and actin assembly. Palladin was recently shown to bind and bundle actin filaments directly. Thus, Beck anticipates that palladin directly interacts with actin to affect actin assembly, and it is the assembly and disassembly of actin filaments that drives invasive motility. By delineating the direct and indirect molecular mechanisms that palladin uses to organize actin arrays, Beck will strive to shed light on the role of palladin in cell motility, podosome formation, and invasion.