A mechanosensory system governs Myosin II accumulation in dividing cells.

摘要

Cytokinesis is a mechanical process in which a cell performs stereotypical shape changes to divide into two daughter cells. Cytokinesis fidelity is crucial for maintaining genetic stability and health of organisms. The precise spatio-temporal regulation of the cytoskelatal network is important for the cells to generate physical forces to perform the shape changes during this process. The mitotic spindle is generally considered the initiator of furrow ingression. However, recent studies suggest that furrows can form without spindles, particularly during asymmetric cell division. In Dictyostelium, the mechanoenzyme myosin II and the actin crosslinker cortexillin I form a mechanosensor that responds to mechanical stress, which could account for spindle-independent contractile protein recruitment at the cleavage furrow. To effectively generate mechanical stress at the cleavage furrow, myosin II has to assemble into bipolar thick filaments. Shifting the myosin II assembly dynamics causes defects in cytokinesis and cell cortex stability, highlighting the important role of myosin II in cell mechanics and force generation. A mechanical stress-responsive system has been identified that integrates the regulatory and contractility networks, thereby governing the myosin II accumulation at the cleavage furrow. This system is composed of myosin II, cortexillin I, IQGAP2, kinesin-6 (kifl2) and INCENP. Myosin II and cortexillin I form the core mechanosensor, and mechanosensitive localization of kif12 and INCENP is mediated by IQGAP2. Additionally, IQGAP2 is antagonized by IQGAP1 to modulate the mechanoresponsiveness of the system, suggesting a possible mechanism for discriminating between mechanical and biochemical inputs. Furthermore, IQGAP2 is important for maintaining spindle morphology and kifl2 and myosin II cleavage furrow recruitment. Cortexillin II is not directly involved in myosin II mechanosensitive accumulation, but without cortexillin I, cortexillin PI's role in membrane-cortex attachment is revealed. Finally, the mitotic spindle is dispensable for the system. Overall, this mechanosensory system is structured like a control system characterized by mechanochemical feedback loops that regulate myosin II localization at sites of mechanical stress and the cleavage furrow.