A5012028857- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Advanced Fluorescence Microscopy Techniques
- Cellular transport and secretion
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Heat shock proteins research
- Fungal and yeast genetics research
Brandeis University
2016-2023
Abstract Actin polymerization powers key cellular processes, including motility, morphogenesis, and endocytosis. The actin turnover cycle depends critically on “re-charging” of ADP-actin monomers with ATP, but whether this reaction requires dedicated proteins in cells, the underlying mechanism, have remained elusive. Here we report that nucleotide exchange catalyzed by ubiquitous cytoskeletal regulator cyclase-associated protein (CAP) is critical for actin-based processes vivo. We determine...
The evolutionarily conserved Arp2/3 complex plays a central role in nucleating the branched actin filament arrays that drive cell migration, endocytosis, and other processes. To better understand regulation, we used single-particle electron microscopy to compare structures of bound three different inhibitory ligands: glia maturation factor (GMF), Coronin, Arpin. Although inhibitors have distinct binding sites on complex, they each induced an "open" nucleation-inactive conformation. Coronin...
Abstract Formation and turnover of branched actin networks underlies cell migration other essential force-driven processes. Type I nucleation-promoting factors (NPFs) such as WASP recruit monomers to Arp2/3 complex stimulate nucleation. In contrast, mechanisms type II NPFs Abp1 (also known HIP55 Drebrin-like protein) are less well understood. Here, we use single-molecule analysis investigate yeast effects on complex, find that strongly enhances Arp2/3-dependent branch nucleation by...
How actin filaments are spatially organized and remodeled into diverse higher-order networks in vivo is still not well understood. Here, we report an unexpected F-actin "coalescence" activity driven by cyclase-associated protein (CAP) enhanced its interactions with actin-binding 1 (Abp1). We directly observe S. cerevisiae CAP Abp1 rapidly transforming branched or linear bundling sliding past each other, maximizing filament overlap, promoting compaction bundles. This does require ATP...