Cortical Dynein Controls Microtubule Dynamics to Generate Pulling Forces that Position Microtubule Asters

SummaryDynein at the cortex contributes to microtubule-based positioning processes such as spindle positioning during embryonic cell division and centrosome positioning during fibroblast migration. To investigate how cortical dynein interacts with microtubule ends to generate force and how this functional association impacts positioning, we have reconstituted the ‘cortical’ interaction between dynein and dynamic microtubule ends in an in vitro system using microfabricated barriers. We show that barrier-attached dynein captures microtubule ends, inhibits growth, and triggers microtubule catastrophes, thereby controlling microtubule length. The subsequent interaction with shrinking microtubule ends generates pulling forces up to several pN. By combining experiments in microchambers with a theoretical description of aster mechanics, we show that dynein-mediated pulling forces lead to the reliable centering of microtubule asters in simple confining geometries. Our results demonstrate the intrinsic ability of cortical microtubule-dynein interactions to regulate microtubule dynamics and drive positioning processes in living cells.PaperClip To listen to this audio, enable JavaScript on your browser. However, you can download and play the audio by clicking on the icon belowHelp with MP3 filesOptionsDownload audio (3418 K)

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (333 K)Download as PowerPoint slideHighlights► Barrier-attached dynein captures microtubule ends and controls microtubule length ► Interaction between dynein and shrinking microtubules generates pulling forces ► Combined pushing and pulling forces reliably center microtubule asters ► Positioning due to pulling is explained by a theoretical model of aster mechanics