title: Dynein tethers and stabilizes dynamic microtubule plus ends.
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. 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. 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.
authors.affiliation: Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6085, USA.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Hendricks
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Lazarus
authors.forename: Eran
authors.initials: E
authors.lastname: Perlson
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Gardner
authors.forename: David J
authors.initials: DJ
authors.lastname: Odde
authors.forename: Yale E
authors.initials: YE
authors.lastname: Goldman
authors.forename: Erika L F
authors.initials: EL
authors.lastname: Holzbaur
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D019295:Computational Biology; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D011994:Recombinant Proteins / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D014404:Tubulin; D000255:Adenosine Triphosphate; D004398:Dyneins