eLife · 2015 · 56 citations · 31 references
Life SciencesCell BiologyMolecular BiologyCell SignalingCytoskeletonSignal TransductionCytoskeletal Associated ProteinsCytoskeletal MechanicsCytoskeletal SignalingMicrotubule-associated ProteinsMitotic SpindleMotor ProteinsKinesin MotorsMicrotubule PolymerizationNegative FeedbackNegative Feedback MechanismsPositive FeedbackPositive Feedback LoopsPositive Feedback MechanismsSpindle Size Control
The size and position of mitotic spindles is determined by the lengths of their constituent microtubules. Regulation of microtubule length requires feedback to set the balance between growth and shrinkage. Whereas negative feedback mechanisms for microtubule length control, based on depolymerizing kinesins and severing proteins, have been studied extensively, positive feedback mechanisms are not known. Here, we report that the budding yeast kinesin Kip2 is a microtubule polymerase and catastrophe inhibitor in vitro that uses its processive motor activity as part of a feedback loop to further promote microtubule growth. Positive feedback arises because longer microtubules bind more motors, which walk to the ends where they reinforce growth and inhibit catastrophe. We propose that positive feedback, common in biochemical pathways to switch between signaling states, can also be used in a mechanical signaling pathway to switch between structural states, in this case between short and long polymers.
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Global analysis of protein expression in yeast
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