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PROJECTS

Actin Filament Networks – Transitions from Branched to Bundled

Cellular actin filaments assemble as dynamic networks of branched, crosslinked and bundled filaments that, together, orchestrate migration, move organelles, establish cell polarity, generate forces and confer mechanical properties.  A spectrum of actin network architectures exists in cells. Two well-characterized networks are 1) the sheet-like networks composed of branched and cross-linked actin filaments that support cellular protrusions, such as lamellipodia of migrating cells, and 2) networks composed of linearly bundled filaments, such as in filopodia or comprising actomyosin of the lamellum.  Our goal is to determine how different types of actin filament networks form and become integrated in time and space to execute whole cell behaviors that depend on them.  We have discovered that the large GTPase, dynamin2, a component of lamellipodial actin networks, influences the assembly of actomyosin networks. We propose that dynamin2 remodels branched lamellipodial actin filaments into filaments that readily form linearly arrayed filaments that optimally co-assemble with myosin II to form actomyosin.  We are testing this hypothesis and aim to define the molecular mechanisms by which dynamin2 remodels actin networks.

Anti-capping and Barbed End Elongation by Ena-VASP proteins

A long-standing interest is to understand the spatial and temporal regulation of dynamic actin filament barbed ends that power many cellular processes. We have focused on actin filament barbed ends because they are the fast-growing end of actin filaments and generally provide the “pushing” force for cellular movements. We have studied two key barbed end regulators: capping protein, a ubiquitous actin-binding protein that regulates filament growth by "capping" the fast-growing barbed end and proteins of the Ena/VASP family, which protect barbed ends from capping in vitro and promote their rapid elongation under specific conditions. We use biochemical assays and TIRF microscopy to decipher the mechanisms whereby capping protein and Ena/VASP proteins regulate actin filament dynamics.