Vliv scaffold proteinu RACK1 a signální dráhy ERK na buněčnou polaritu

Klímová, Zuzana

The establishment of cell polarity is an essential step in cell migration, as it provides cells with information about the direction of migration. It is a highly dynamic process that leads to an asymmetric distribution of cytoskeletal networks, cell organelles, protein complexes and signalling pathways, which is reflected in the typical polarised cell shape. The cell shape is determined by the interplay between the dynamics of the actin cytoskeleton, cell adhesions and the cell membrane towards the extracellular surface. Cell adhesion and spreading on the extracellular matrix is a morphogenetic process in which cells initially spread isotropically from the point of first contact and then spontaneously break their radial symmetry and develop a migratory polarity with spatially separated protruding cell front and non-protruding cell rear. It is unclear how these symmetry break events, both complex and stochastic, are organised and regulated. In this study, I show that symmetry breaking in isotropically spreading fibroblasts begins with the establishment of a non-protruding cell rear delineated by large but sparse focal adhesions. Development of the non-protruding regions requires the scaffold protein RACK1, which promotes adhesion-mediated activation of ERK2. ERK2 and RACK1 inhibit p190RhoGAP...

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