As one of the most abundant proteins in the cell, actin participates in many important cellular processes including cell motility, maintenance of cell shape, cell division, and muscle contraction. Coordination of these diverse cellular processes therefore requires responsive regulation of actin. Currently over 150 actin-binding proteins have been identified which influence localization, polymerization dynamics, crosslinking, and organization of actin. Cytoskeletal actin is important for normal cellular function, however it can also be subverted in cancer and contributes to changes in cell motility and invasiveness.

Palladin is a recently identified protein from a novel family of actin binding proteins that has emerged as a key player in organizing actin arrays within migrating cells. Overexpression of palladin has been linked to highly metastatic cancers such as breast and pancreatic. Palladin family members utilize immunoglobulin-like (Ig) domains to bind and crosslink actin, highlighting a new role for Ig domains. Our preliminary results suggest yet another novel role for palladin that may include both promoting actin polymerization and/or modifying the structure of actin filaments.

Recently, mutations in the muscle protein myopalladin have been linked to the pathogenesis of cardiomyopathy. While myopalladin is thought to play a role in regulating the organization of sarcomere structure within cardiac and skeletal muscles, insufficient knowledge of myopalladin’s interactions with other key molecules has hampered development of new therapies for cardiomyopathies.  Mutations in myopalladin cause diverse cardiomyopathic phenotypes that are poorly understood; therefore, our goal is to understand the relationship between structural and biochemical alterations in cellular and molecular mechanisms underlying sarcomere organization, regulation and function

Current research interests in the Beck group are to investigate the mechanisms by which palladin and myopalladin, through both direct and indirect molecular mechanisms, affects actin dynamics. Specifically, we will use biochemical and cell biological approaches, coupled with protein structural studies to elucidate the role and mechanisms for how the novel, actin crosslinking protein palladin and myopalladin influences the actin cytoskeleton. We intend to elucidate in detail the biochemical mechanisms of actin regulation and organization using kinetic assays of actin polymerization coupled with studies of protein-protein interactions via NMR.

TIRF Microscopy allows us to visualize individual actin filaments grow in real time. So we can compare the amount of filament growth and the resulting structures of the actin filaments in the presence and absence of palladin.