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Growth Cone-Localized Microtubule Organizing Center Establishes Microtubule Orientation in Dendrites

68 Pages Posted: 15 Jan 2020 Sneak Peek Status: Under Review

See all articles by Xing Liang

Xing Liang

Stanford University - Department of Biology

Marcela Kokes

Stanford University - Department of Biology

Richard Fetter

Stanford University - Howard Hughes Medical Institute

Maria D. Sallee

Stanford University - Department of Biology

Adrian W. Moore

RIKEN Center for Brain Science

Jessica Feldman

Stanford University - Department of Biology

Kang Shen

Stanford University - Department of Biology

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Abstract

A polarized arrangement of neuronal microtubule arrays is the foundation of membrane trafficking and subcellular compartmentalization. Conserved among both invertebrates and vertebrates, axons contain exclusively “plus-end-out” microtubules while dendrites contain a high percentage of “minus-end-out” microtubules, the origins of which have been a mystery. Here we show that the dendritic growth cone contains a non-centrosomal microtubule organizing center, which generates minus-end-out microtubules along outgrowing dendrites and plus-end-out microtubules in the growth cone. RAB-11-positive endosomes accumulate in this region and are responsible for localizing the microtubule nucleation complex γ-TuRC. The MTOC tracks the extending growth cone by kinesin-1/UNC-116-mediated endosome movements on distal plus-end-out microtubules and dynein clusters this advancing MTOC. Critically, perturbation of the function or localization of the MTOC causes reversed microtubule polarity in dendrites. These findings unveil the dendritic MTOC as a critical organelle for establishing axon-dendrite polarity.

Keywords: neuronal cell polarity, Dendrite development, Microtubule organization, γ-TuRC, non-centrosomal microtubule organizing center

Suggested Citation

Liang, Xing and Kokes, Marcela and Fetter, Richard and Sallee, Maria D. and Moore, Adrian W. and Feldman, Jessica and Shen, Kang, Growth Cone-Localized Microtubule Organizing Center Establishes Microtubule Orientation in Dendrites. NEURON-D-19-02130. Available at SSRN: https://ssrn.com/abstract=3519576 or http://dx.doi.org/10.2139/ssrn.3519576
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Xing Liang

Stanford University - Department of Biology ( email )

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Marcela Kokes

Stanford University - Department of Biology

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Richard Fetter

Stanford University - Howard Hughes Medical Institute

Stanford, CA 94305
United States

Maria D. Sallee

Stanford University - Department of Biology

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Adrian W. Moore

RIKEN Center for Brain Science

2-1 Hirosawa
Saitama, Saitama 351-0198
Japan

Jessica Feldman

Stanford University - Department of Biology ( email )

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

Kang Shen (Contact Author)

Stanford University - Department of Biology

Gilbert Building, Rm 109
371 Serra Mall
Stanford, CA 94305
United States

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