AG Rothkegel

Research interests:

• Functional diversity of profilin isoforms in different cell systems
• Regulation of actin-based neuronal plasticity

Profilins are essential regulators of actin dynamics in all eukaryotes and they bind to monomeric actin in a 1:1 complex. In addition, profilins can bind to the polyproline stretches of formins, Ena/VASP and other proteins, and to acidic phospholipids, some of which are also involved in signal transduction. Hence, profilins are thought to be engaged in linking signal transduction to actin filament formation, and in accordance with this view, they were found to localize with actin, VASP, WAVE and formins in membrane-apposed, dynamic regions of cells.

The different actin-based motility processes in cells requires regional modulation and specific fine-tuning of profilin-ligand interactions. Thus, different phospholipids and polyproline ligands as well as different actin isoforms and profilins might specialize in various motility processes. Consistent with such a concept is the notion that profilins occur in a number of isoforms that show tissue-specific expression. In mammals, four discrete profilin genes give rise to five different isoforms.

Profilin-1 (PFN1) is ubiquitously expressed and is apparently engaged in general motility functions, such as cell migration, cytokinesis and adhesion. Profilin- 2a (PFN2a), the major splice form of profilin-2, is primarily expressed in the brain, whereas a minor splice product, PFN2b, was identified in the kidney. Furthermore, PFN3 and PFN4 were identified in mammalian, where PFN4 seems specifically involved in the maturation of spermatids.
Isoform-specific functional roles of mammalian profilins have been mainly investigated in the CNS of mice and rats. PFN1 was suggested to modulate neuronal actin dynamics during neuritogenesis, whereas two possible functions are under debate for PFN2a, first, an engagement of PFN2a in the structural plasticity of synapses and second, a regulatory function of PFN2a in endo- and exocytosis of neurons.
Our current work is focused on elucidating the functional diversity of profilin isoforms in different cell systems and on unraveling the underlying molecular mechanisms regulating the microfilament system in synaptic plasticity.