Research project Cell Motility and the role of Profilin
This project reflects a long-standing interest in eukaryotic cell motility, i.e. movements of intracellular structures and migration of whole cells. Profilin is a coordinator of the two principal force generating machineries behind virtually all cell motility as first revealed by us and therefore takes a special interest in our studies.
For their viability, all eukaryotic cells depend on force-generating machineries formed by actin and tubulin. These proteins separately build dynamic organizations of polymers that span the interior of cells and interact with a cohort of other molecules some of which such as myosins in the case of actin filaments and kinesins and dyneins in the case of microtubules are direcly involved the force-generating process. Additionally, force is also generated by the formation – polymerization – of the filament structures. Particularly actin filaments are under continuous re-organization in many interior areas of the cell. For instance, is their rapid turn-over at cell edges a major mechanism behind the capacity of cells to form fine protrusions at their periphery, protrusions used for interactions with other cells or with their substratum. This is a strickly controlled activity both in time and space, and here profilin plays a crucial role controlling the actin filament growth and, as first shown by us, also the formation and growth of microtubules. Thus profilin is an important component, contributing to the coordination of of actin filament and mictrotubule organization.
Members of the project
During the years a large number of PhD- and postdoctor students have made significant contributions to the development of this project. The most recent observation, characterizing profilin as a regulator of microtubule nucleation and elongation largely resulted from work by Michela Nejedla and Sara Sadi. All other names can be found in the author lines of the attached publication list.
Project description
Several contributions have been during this project that have added significantly to the understanding of the molecular cell biology of actin, the microfilament system and cell motiliy. Establishment and further refinement of an expression system for non-muscle actin (refs herwid) led to several detailed studies of actin biochemistry (e.g Nyman et al, 2002). Parallel studies of profilin alone and in complex with actin – profilin-actin – both in vitro and in vivo led to the construction of a non-dissociable and therefore non-dynamic complex of profilin-actin (Nyman et al, 2002). Microinjection this complex into cells demonstrated the importance of profilin-actin as actin source and crucial for actin polymerization (Hajkowa et al 2000; Grenklo et al 2003; Wen et al 2016). Observing that profilin antibodies decorated microtubules (Grenklo et al 2004) and further insights of a tight connection between microtubules and profilin (Johnsson and Karlsson, 2010) initiated work that eventually led to the discovery of profilin as a regulator of microtubule nucleation and elongation (Nejedla et al 2016; Nejedla et al 2017, Nejedla et al 2021; Karlsson and Draber). Parallel studies to the above demonstrated that subunits of the molecular chaperone CCT, which is required for actin to attain a native conformation influence actin function beyond their role in actin folding (Spiess et al 2015; Elliot et al, 2015). Current activities are concentrated to the role of profilin, its interplay with other actin regulatory components and its function for coordination of distribution and dynamics of actin and microtubules.