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Korkmazhan, E.

Publications and source records attributed to Korkmazhan, E..

2 recordsLinked to original sources

Extraction of accurate cytoskeletal actin velocity distributions from noisy measurements

Dynamic remodeling of the actin cytoskeleton is essential for many cellular processes. Tracking the movement of individual actin filaments can in principle shed light on how this complex behavior arises at the molecular level. However, the information that can be extracted from these measurements is often limited by low signal-to-noise ratios. We developed a Bayesian statistical approach to estimate true, underlying velocity distributions from the tracks of individual actin-associated fluorophores with quantified localization uncertainties. We found that filamentous (F)-actin velocity distributions in fibroblasts and endothelial cells were well described by a statistical jump process, in which filaments exist in mechanical equilibria punctuated by abrupt, jump-like movements. A model with exponentially distributed jump length- and time-scales recapitulated actin filament velocity distributions measured for the cell cortex, integrin-based adhesions, and stress fibers, suggesting that a common physical model can potentially describe actin filament dynamics in a variety of cellular contexts.

biophysics

Limited Dishevelled/Axin oligomerization determines efficiency of Wnt/β-catenin signal transduction

In Wnt/{beta}-catenin signaling, the transcriptional coactivator {beta}-catenin is regulated by its phosphorylation in a complex that includes the scaffold protein Axin and associated kinases. Wnt binding to its coreceptors activates the cytosolic effector Dishevelled (Dvl), leading to the recruitment of Axin and the inhibition of {beta}-catenin phosphorylation. This process requires interaction of homologous DIX domains present in Dvl and Axin, but is mechanistically undefined. We show that Dvl DIX forms antiparallel, double-stranded oligomers in vitro, and that Dvl in cells forms oligomers typically <10 molecules at endogenous expression levels. Axin DIX (DAX) forms small single-stranded oligomers, but its self-association is stronger than that of DIX. DAX caps the ends of DIX oligomers, such that a DIX oligomer has at most four DAX binding sites. The relative affinities and stoichiometry of the DIX-DAX interaction provide a mechanism for efficient inhibition of {beta}-catenin phosphorylation upon Axin recruitment to the Wnt receptor complex.

biochemistry