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

• Published in: Cell Vol. 148; no. 3; pp. 502 - 514
• Main Authors: Laan, Liedewij, Pavin, Nenad, Husson, Julien, Romet-Lemonne, Guillaume, van Duijn, Martijn, López, Magdalena Preciado, Vale, Ronald D., Jülicher, Frank, Reck-Peterson, Samara L., Dogterom, Marileen
• Format: Journal Article
• Language: English
• Published: 03.02.2012
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2012.01.007

Dynein-mediated pulling forces generated on dynamic microtubule ends at the cortex contribute to cellular positioning processes such as spindle positioning during embryonic cell division and centrosome positioning during fibroblast migration. The details of dynein’s interaction with microtubule ends, and its consequences for positioning processes remain however unclear. 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.