Department of Biophysical Chemistry
Medizinische Hochschule Hannover
email: Jan Faix
The actin cytoskeleton is a fascinating, highly dynamic structure that allows cells for instance to adopt a specific morphology and to move on a substrate or within tissues. The force required to accomplish these tasks comes first and foremost from the highly regulated polymerization of actin monomers into filaments, which in turn can be further organized into more complex arrays by a plethora of accessory proteins. Concomitantly, actin filaments are dissembled into monomers to replenish the actin monomer pool.
We are employing a combinatory approach of biochemistry, biophysics, cell biology and imaging to better understand the molecular basis of a number of fundamental actin-based processes underlying cell motility and the formation of specific cell protrusion such as filopodia or lamellipodia as well as phagocytosis and cell division in Dictyostelium and mammalian cells.
Currently, our research is mainly focused on the molecular machineries required for the formation and disassembly of filopodia. These highly dynamic finger-like protrusions are composed of actin filaments aligned in tight parallel bundles with their fast growing barbed ends pushing against the plasma membrane.
Filopodia are used by many cell types as sensing organs to explore environmental cues, and they have also been implicated in cell motility, zippering of epithelial sheets during morphogenesis as well as in cell-substrate adhesion and the spread of viruses. Notwithstanding with this our knowledge about the molecular inventory of proteins involved and the molecular mechanisms underlying filopodia formation are still incomplete.
Currently, we focus on the characterization of the molecular interplay between formins, Ena/VASP proteins and known accessory proteins during the formation and disassembly to filopodia. Formins nucleate and elongate linear actin filaments and have been shown to play a critical role in the formation of filopodia.
Other factors regulating actin assembly in filopodia, lamellipodia and on the surface of pathogens are Ena/VASP proteins. By analysis of actin assembly by TIRF microscopy on the single filament level we recently showed that both, human and Dictyostelium VASP, are directly involved in mediating processive filament elongation by the delivery of actin monomers to growing filament barbed end. Thus, Ena/VASP proteins constitute the second known filament elongators besides formins. A challenging task in the future is to determine the specific contribution of Ena/VASP proteins and formins to nucleation and elongation of filopodial actin filaments.