The long-term objectives of this research are to understand the functional and mechanistic relationships between actin dynamics and membrane traffic. Convincing evidence supports such a relationship, however, in spite of this evidence, the nature of this relationship remains obscure. We propose a combination of cellular and biochemical experiments to test hypotheses about the molecular mechanisms and biological functions provided by actin filaments during membrane traffic. The GTPase, dynamin, a primary regulator of endocytosis in mammalian cells, has emerged as a one molecule that might coordinately regulate actin and membrane dynamics. Dynamic actin is maintained by factors that promote filament assembly, by factors that define the length and organization of filaments, by factors that disassemble filaments and by factors that replenish the ATP-monomer pool. Dynamin could influence actin through one or more of these routes. One specific goal of this research is to elucidate the mechanisms by which dynamin regulates actin dynamics in vivo. We will achieve this goal by determining how mutants of dynamin having well-defined biochemical properties affect actin dynamics in vivo. Clues obtained from these observations in living cells will guide biochemical experiments using purified proteins and cell-free extracts to test hypotheses for the mechanisms. A second goal is to define the temporal and spatial relationship of dynamic actin and the dynamics of recycling membrane traffic and to determine how recycling pathways depend on actin. These pursuits will advance our understanding of membrane homeostasis during the dynamic cellular processes of cell migration and endocytosis.
| Menon, Manisha; Askinazi, Olga L; Schafer, Dorothy A (2014) Dynamin2 organizes lamellipodial actin networks to orchestrate lamellar actomyosin. PLoS One 9:e94330 |
| Kim, Ji Hoon; Cho, Aeri; Yin, Hongyan et al. (2011) Psidin, a conserved protein that regulates protrusion dynamics and cell migration. Genes Dev 25:730-41 |
| Mooren, Olivia L; Schafer, Dorothy A (2009) Constricting membranes at the nano and micro scale. Proc Natl Acad Sci U S A 106:20559-60 |
| Mooren, Olivia L; Kotova, Tatyana I; Moore, Andrew J et al. (2009) Dynamin2 GTPase and cortactin remodel actin filaments. J Biol Chem 284:23995-4005 |
| Cai, Liang; Makhov, Alexander M; Schafer, Dorothy A et al. (2008) Coronin 1B antagonizes cortactin and remodels Arp2/3-containing actin branches in lamellipodia. Cell 134:828-42 |
| Pasic, Lejla; Kotova, Tatyana; Schafer, Dorothy A (2008) Ena/VASP proteins capture actin filament barbed ends. J Biol Chem 283:9814-9 |
| Cai, Liang; Marshall, Thomas W; Uetrecht, Andrea C et al. (2007) Coronin 1B coordinates Arp2/3 complex and cofilin activities at the leading edge. Cell 128:915-29 |
| Bensenor, Lorena B; Kan, Ho-Man; Wang, Ningning et al. (2007) IQGAP1 regulates cell motility by linking growth factor signaling to actin assembly. J Cell Sci 120:658-69 |
| Barzik, Melanie; Kotova, Tatyana I; Higgs, Henry N et al. (2005) Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteins. J Biol Chem 280:28653-62 |
| Schafer, Dorothy A (2004) Regulating actin dynamics at membranes: a focus on dynamin. Traffic 5:463-9 |
