Dynein tethers and stabilizes dynamic microtubule plus ends

Adam G. Hendricks, Jacob E. Lazarus, Eran Perlson, Melissa K. Gardner, David J. Odde, Yale E. Goldman, Erika L.F. Holzbaur

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Microtubules undergo alternating periods of growth and shortening, known as dynamic instability. These dynamics allow microtubule plus ends to explore cellular space. The "search and capture" model posits that selective anchoring of microtubule plus ends at the cell cortex may contribute to cell polarization, spindle orientation, or targeted trafficking to specific cellular domains [1-3]. Whereas cytoplasmic dynein is primarily known as a minus-end-directed microtubule motor for organelle transport, cortically localized dynein has been shown to capture and tether microtubules at the cell periphery in both dividing and interphase cells [3-7]. To explore the mechanism involved, we developed a minimal in vitro system, with dynein-bound beads positioned near microtubule plus ends using an optical trap. Dynein induced a significant reduction in the lateral diffusion of microtubule ends, distinct from the effects of other microtubule-associated proteins such as kinesin-1 and EB1. In assays with dynamic microtubules, dynein delayed barrier-induced catastrophe of microtubules. This effect was ATP dependent, indicating that dynein motor activity was required. Computational modeling suggests that dynein delays catastrophe by exerting tension on individual protofilaments, leading to microtubule stabilization. Thus, dynein-mediated capture and tethering of microtubules at the cortex can lead to enhanced stability of dynamic plus ends.

Original languageEnglish (US)
Pages (from-to)632-637
Number of pages6
JournalCurrent Biology
Volume22
Issue number7
DOIs
StatePublished - Apr 10 2012

Bibliographical note

Funding Information:
We thank Benjamin Stevens and Pritish Argawal for scientific and technical assistance. This work was supported by NIH grant GM48661 to E.L.F.H., NIH grant GM71522 and NSF grant 0615568 to D.J.O., a Muscular Dystrophy Association postdoctoral fellowship to E.P., an NIH postdoctoral fellowship to A.G.H., and an NIH predoctoral fellowship to J.E.L. The optical trap was funded by NSF Nanotechnology Science and Engineering Center grant DMR04-25780 and NIH grant GM087253.

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