Abstract
Tissue maintenance and development requires a directed plane of cell division. While it is clear that the division plane can be determined by retraction fibres that guide spindle movements, the precise molecular components of retraction fibres that control spindle movements remain unclear. We report MARK2/Par1b kinase as a novel component of actin-rich retraction fibres. A kinase-dead mutant of MARK2 reveals MARK2's ability to monitor subcellular actin status during interphase. During mitosis, MARK2's localization at actin-rich retraction fibres, but not the rest of the cortical membrane or centrosome, is dependent on its activity, highlighting a specialized spatial regulation of MARK2. By subtly perturbing the actin cytoskeleton, we reveal MARK2's role in correcting mitotic spindle off-centring induced by actin disassembly. We propose that MARK2 provides a molecular framework to integrate cortical signals and cytoskeletal changes in mitosis and interphase.
Highlights
Tissue development and regeneration requires a close coordination of cell division and cell polarity regulatory pathways
We report MARK2/Par1b, a known regulator of microtubule stability, as a novel component of retraction fibres with a role in correcting spindle off-centring induced by actin disassembly
Its dynamic localization at the mitotic cell cortex is independent of cortical dynein, astral microtubules and the actin network, highlighting its upstream position among the regulators of spindle movements
Summary
Tissue development and regeneration requires a close coordination of cell division and cell polarity regulatory pathways. Among the four human Par kinases (MARK 1–4), MARK2/hPar1b is uniquely important for establishing the plane of division and it achieves this through two modes: a cell polarity-dependent mode and a cell polarityindependent but cell shape-determined mode [3,4,5]. In both cases, MARK2 controls the position of the mitotic spindle, as seen in a variety of non-polarized and polarized systems, including human cervical epithelial cell cultures, hepatocyte lumina and columnar epithelia [3,4,5,6]. While cell polarity pathways control spindle positioning by asymmetric enrichment of cortical dynein, how interphase cell shape determines spindle positioning in non-polarized cultures is not fully clear (reviewed in [7,8])
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