YAP/TAZ dynamics

YAP/TAZ is regulated by both stress fiber/RhoA activity and cell-cell contacts/LATS activity (2). It translocates to the nucleus to bind with transcription factors such as TEAD and activates them. Phosphorylation by LATS or, potentially through some currently unknown kinase whose activity is regulated by cytoskeletal tension, leads to sequestration of YAP/TAZ. We thus model nuclear YAP/TAZ concentrations by

Here, k_CN is the rate of YAP/TAZ translocating from the cytoplasm to the nucleus with no active cytoplasmic F-actin and myosin; k_NC is the rate of YAP/TAZ translocating from nucleus to cytoplasm with no active LATS; and k_CY is the YAP/TAZ nuclear translocation rate due to the stress fibers or the tensional cytoplasmic F-actin. The value n characterizes the weight of how YAP/TAZ activity is dependent on cytoplasmic F-actin. The value n = 1 is the default setting that indicates the myosin and cytoplasmic F-actin have a similar effect on regulating YAP/TAZ activity, and k_ly is the cytoplasmic translocation rate of YAP/TAZ due to active LATS. The mechanism for YAP/TAZ nuclear import/export is unknown (2), thus we model the YAP/TAZ nuclear transport directly depending on the stress fibers and LATS as approximation. Importantly, YAP/TAZ nuclear translocation has been shown to be dependent on stress fibers and RhoA in 2D (8). In 3D, stress fibers in cells are not as distinct as those present in the 2D monolayer cultures (59, 60), but still with more F-actin in the cytoplasm in rigid environments in comparison to the softer ones (61). Thus for cells with no apparent stress fiber structure in 3D, we generally use the tensional cytoplasmic F-actin filaments, which are characterized by the product of the cytoplasmic F-actin concentration and active myosin concentration Fcyto(t)myo_A(t), to be an equivalent component of stress fibers in 3D.