Motegi, F. | Search bioRxiv

bioRxiv2018

ZO-2 induces cytoplasmic retention of YAP by promoting a LATS1-ZO-2-YAP complex at tight junctions

Contact inhibition of proliferation (CIP) is a key mechanism that transduces the cell density status of tissue and organs into a unique transcriptional program by translocating YAP between the nucleus and the cytoplasm. However, the nature of the cell density-dependent cues that regulate the YAP distribution remains unclear. Here, we present evidence that tight junctions serve as a platform that controls both distribution and activity of LATS1, a kinase that phosphorylates YAP. This CIP effect is mediated by the scaffold function of junctional protein, ZO-2, by promoting LATS1 interaction with YAP in the cytoplasm, and then targeting the tripartite complex to tight junctions. There, LATS1 is activated by angiomotin and NF2, thereby stimulating YAP phosphorylation and its cytoplasmic retention. Our findings delineate novel mechanisms governing CIP, in which ZO-2 utilizes the status of cell-cell cohesion to control the phosphorylation status and therefore inactivation of YAP by LATS1 in the cytoplasm.

cell biology↗

bioRxiv2017

TPXL-1 Activates Aurora A to Clear Contractile Ring Components from the Polar Cortex During Cytokinesis

During cytokinesis, a signal from the bundled microtubules that form between the separating anaphase chromosomes promotes the accumulation of contractile ring components at the cell equator, while a signal from the centrosomal microtubule asters inhibits accumulation of contractile ring components at the cell poles. However, the molecular identity of the inhibitory signal has remained unknown. To identify molecular components of the aster-based inhibitory signal, we developed a means to monitor the removal of contractile ring proteins from the polar cortex after anaphase onset. Using this assay, we show that polar clearing is an active process that requires activation of Aurora A kinase by TPXL-1. TPXL-1 concentrates on astral microtubules coincident with polar clearing in anaphase, and its ability to recruit Aurora A and activate its kinase activity are essential for clearing. In summary, our data identify Aurora A kinase as an aster-based inhibitory signal that restricts contractile ring components to the cell equator during cytokinesis.\n\nSUMMARYDuring cytokinesis, centrosomal asters inhibit cortical contractility at the cell poles. Mangal et al. provide molecular insight into this phenomenon, showing that TPXL-1, which localizes to astral microtubules, activates Aurora A kinase to clear contractile ring proteins from the polar cortex.

cell biology↗