A08
Project Area A - Biology and Molecular Oncology
Prof. Dr. Perihan Nalbant
Molecular Cell Biology
University of Duisburg-Essen
Phone: +49 201 183 3206
Email
Switching of spatio-temporal Rho GTPase signal network dynamics during cell cycle phase transitions
Cells dynamically alter their shape to facilitate profound state transitions during the cell cycle. These morphological changes are driven by dynamic rearrangements of the actin cytoskeleton under the control of the Rho GTPases, Rho, Rac and Cdc42. In non-dividing cells, we recently identified a signal network that combines positive and negative feedback regulation to generate subcellular Rho activity pulses, and we now find that these activity dynamics change during the morphological switches between interphase, mitosis and cytokinesis. Here, we will use advanced microscopy and acute optogenetic modulation to study spatio-temporal Rho GTPase activity dynamics during mitotic transitions, and we will investigate how this is controlled by the activating Rho GEFs Ect-2 and Lbc-type GEFs. In particular, we will investigate the mutual regulation of these GEFs and study how phosphorylation by mitotic kinases affects the interplay between GEFs and Rho activity. In addition, we will explore in what way distinct spatio-temporal Rho activity dynamics govern the metastatic switch in tumours and the emergence of invasive cell behaviour. Thus, our studies will unravel the function of spatio-temporal Rho activity dynamics and their complex regulation by GEFs in cell cycle transitions and their role in physiological and pathophysiological context.
Project Members
Dr. Kristina Mrug
Katarina Blazevic
Nicole Schrenke
Publications
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Cdc42 activity in the trailing edge is required for persistent directional migration of keratinocytesIn: Molecular Biology of the Cell Vol. 35 (2023) Nr. 1, br1Online Full Text: dx.doi.org/
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Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasisIn: Cell Reports Vol. 37 (2021) Nr. 8, 110056Online Full Text: dx.doi.org/ Online Full Text (Open Access)