Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration

Zhuo Gan; Liya Ding; Christoph J. Burckhardt; Jason Lowery; Assaf Zaritsky; Karlyndsay Sitterley; Andressa Mota; Nancy Costigliola; Colby G. Starker; Daniel F. Voytas; Jessica Tytell; Robert D. Goldman; Gaudenz Danuser

doi:10.1016/j.cels.2016.08.007

Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration

Zhuo Gan, Liya Ding, Christoph J. Burckhardt, Jason Lowery, Assaf Zaritsky, Karlyndsay Sitterley, Andressa Mota, Nancy Costigliola, Colby G. Starker, Daniel F. Voytas, Jessica Tytell, Robert D. Goldman, Gaudenz Danuser^*

^*Corresponding author for this work

Cell & Developmental Biology

Research output: Contribution to journal › Article › peer-review

142 Scopus citations

Abstract

Increased expression of vimentin intermediate filaments (VIFs) enhances directed cell migration, but the mechanism behind VIFs’ effect on motility is not understood. VIFs interact with microtubules, whose organization contributes to polarity maintenance in migrating cells. Here, we characterize the dynamic coordination of VIF and microtubule networks in wounded monolayers of retinal pigment epithelial cells. By genome editing, we fluorescently labeled endogenous vimentin and α-tubulin, and we developed computational image analysis to delineate architecture and interactions of the two networks. Our results show that VIFs assemble an ultrastructural copy of the previously polarized microtubule network. Because the VIF network is long-lived compared to the microtubule network, VIFs template future microtubule growth along previous microtubule tracks, thus providing a feedback mechanism that maintains cell polarity. VIF knockdown prevents cells from polarizing and migrating properly during wound healing. We suggest that VIFs’ templating function establishes a memory in microtubule organization that enhances persistence in cell polarization in general and migration in particular.

Original language	English (US)
Pages (from-to)	252-263.e8
Journal	Cell Systems
Volume	3
Issue number	3
DOIs	https://doi.org/10.1016/j.cels.2016.08.007
State	Published - Sep 28 2016

Funding

This study was supported by NIH grant P01GM096971 (to G.D. and R.G.), CPRIT recruitment award R1225 (to G.D.), and fellowships from the Swiss National Science Foundation and the Novartis Research Foundation (to C.J.B.). We thank the Live Cell Imaging Core Facility at the University of Texas Southwestern Medical Center and the Nikon Imaging Centers at Harvard Medical School and Northwestern University for help with light microscopy, and we thank the Dana Farber Cancer Institute Flow Cytometry core for help with cell sorting. Research reported in this publication was supported by the National Cancer Institute of the NIH under award number 5P30CA142543. We thank Xiao Ma, UTSW, for help with the double-blind analysis of single cell migration.

ASJC Scopus subject areas

Pathology and Forensic Medicine
Histology
Cell Biology

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Gan, Z., Ding, L., Burckhardt, C. J., Lowery, J., Zaritsky, A., Sitterley, K., Mota, A., Costigliola, N., Starker, C. G., Voytas, D. F., Tytell, J., Goldman, R. D., & Danuser, G. (2016). Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration. Cell Systems, 3(3), 252-263.e8. https://doi.org/10.1016/j.cels.2016.08.007

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title = "Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration",

abstract = "Increased expression of vimentin intermediate filaments (VIFs) enhances directed cell migration, but the mechanism behind VIFs{\textquoteright} effect on motility is not understood. VIFs interact with microtubules, whose organization contributes to polarity maintenance in migrating cells. Here, we characterize the dynamic coordination of VIF and microtubule networks in wounded monolayers of retinal pigment epithelial cells. By genome editing, we fluorescently labeled endogenous vimentin and α-tubulin, and we developed computational image analysis to delineate architecture and interactions of the two networks. Our results show that VIFs assemble an ultrastructural copy of the previously polarized microtubule network. Because the VIF network is long-lived compared to the microtubule network, VIFs template future microtubule growth along previous microtubule tracks, thus providing a feedback mechanism that maintains cell polarity. VIF knockdown prevents cells from polarizing and migrating properly during wound healing. We suggest that VIFs{\textquoteright} templating function establishes a memory in microtubule organization that enhances persistence in cell polarization in general and migration in particular.",

author = "Zhuo Gan and Liya Ding and Burckhardt, {Christoph J.} and Jason Lowery and Assaf Zaritsky and Karlyndsay Sitterley and Andressa Mota and Nancy Costigliola and Starker, {Colby G.} and Voytas, {Daniel F.} and Jessica Tytell and Goldman, {Robert D.} and Gaudenz Danuser",

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Gan, Z, Ding, L, Burckhardt, CJ, Lowery, J, Zaritsky, A, Sitterley, K, Mota, A, Costigliola, N, Starker, CG, Voytas, DF, Tytell, J, Goldman, RD & Danuser, G 2016, 'Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration', Cell Systems, vol. 3, no. 3, pp. 252-263.e8. https://doi.org/10.1016/j.cels.2016.08.007

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AU - Ding, Liya

AU - Burckhardt, Christoph J.

AU - Lowery, Jason

AU - Zaritsky, Assaf

AU - Sitterley, Karlyndsay

AU - Mota, Andressa

AU - Costigliola, Nancy

AU - Starker, Colby G.

AU - Voytas, Daniel F.

AU - Tytell, Jessica

AU - Goldman, Robert D.

AU - Danuser, Gaudenz

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N2 - Increased expression of vimentin intermediate filaments (VIFs) enhances directed cell migration, but the mechanism behind VIFs’ effect on motility is not understood. VIFs interact with microtubules, whose organization contributes to polarity maintenance in migrating cells. Here, we characterize the dynamic coordination of VIF and microtubule networks in wounded monolayers of retinal pigment epithelial cells. By genome editing, we fluorescently labeled endogenous vimentin and α-tubulin, and we developed computational image analysis to delineate architecture and interactions of the two networks. Our results show that VIFs assemble an ultrastructural copy of the previously polarized microtubule network. Because the VIF network is long-lived compared to the microtubule network, VIFs template future microtubule growth along previous microtubule tracks, thus providing a feedback mechanism that maintains cell polarity. VIF knockdown prevents cells from polarizing and migrating properly during wound healing. We suggest that VIFs’ templating function establishes a memory in microtubule organization that enhances persistence in cell polarization in general and migration in particular.

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Vimentin Intermediate Filaments Template Microtubule Networks to Enhance Persistence in Cell Polarity and Directed Migration

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