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Redox, profilin, and tropomyosins in the control of the MF System

Behaviour and differentiation of cells are steered by cell:cell communication, and by the interactions cells have with soluble or insoluble components in their surroundings. Transmembrane proteins, growth factor receptors, adhesion proteins, and ion channels, play a central role in this communication. Their signals to the interior of the cell activate the motile machinery of the cell and increase the rate of proliferation. Motile activity is generated by a highly dynamic, and well organized, weave of actin microfilaments (MF) connected to the inside of the cell membrane. Although there has been great progress in our understanding of the physiological importance of the MF-system, many aspects are still unclear. It has been reported that generation of reactive oxygen species (ROS; H2O2) in cells might control the MF-system, and the roles of ROS in disease, including autism and cancer, is emerging fields of research. An understanding of the role of hydrogen peroxide (H2O2) in the regulation of proteins of the MF-system (actin, profilin, and tropomyosin) is urgently needed.

Dendritic spines at postsynaptic contacts of excitatory neurons depend on polymerization of actin, and synaptic deficiencies and neuronal migration defects have been identified as causes of hippocampal and amygdalar dysfunctions linked to autism. Furthermore, tumorigenicity is highly correlated with changes in the organization and activity of the MF-system. H2O2 is essential to growth factor-induced signaling, since ROS quenching abolishes its effects, and PTEN, a tumor suppressor protein, linked to the MF-system is directly controlled by oxidation. Inactivation of PTEN results in uncontrolled motility. Lindberg’s group has shown that actin, like profilin and tropomyosin, is sensitive to oxidation. With this project the hope was to contribute to the understanding of the function of the MF-system in normal and dysfunctional cells.