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PMID: 27764672 Published · ppublish English Journal Article

Microtubule Organization Determines Axonal Transport Dynamics.

Neuron ·Vol. 92 ·No. 2 ·2016-10-19 ·Pages 449-460

Yogev S, Cooper R, Fetter R, Horowitz M, Shen K

Abstract

Axonal microtubule (MT) arrays are the major cytoskeleton substrate for cargo transport. How MT organization, i.e., polymer length, number, and minus-end spacing, is regulated and how it impinges on axonal transport are unclear. We describe a method for analyzing neuronal MT organization using light microscopy. This method circumvents the need for electron microscopy reconstructions and is compatible with live imaging of cargo transport and MT dynamics. Examination of a C. elegans motor neuron revealed how age, MT-associated proteins, and signaling pathways control MT length, minus-end spacing, and coverage. In turn, MT organization determines axonal transport progression: cargoes pause at polymer termini, suggesting that switching MT tracks is rate limiting for efficient transport. Cargo run length is set by MT length, and higher MT coverage correlates with shorter pauses. These results uncover the principles and mechanisms of neuronal MT organization and its regulation of axonal cargo transport.

Keywords
C. elegans axonal transport dynein kinesin microtubule microtubule dynamics microtubule length microtubule organization
MeSH Terms
Animals Axonal Transport Caenorhabditis elegans Cytoskeleton/metabolism Dyneins/metabolism Kinesins/metabolism Microscopy Microtubule-Associated Proteins/metabolism Microtubules/metabolism,ultrastructure Motor Neurons/metabolism,ultrastructure Polymers/metabolism Signal Transduction Time-Lapse Imaging
Chemicals
Microtubule-Associated Proteins Polymers Dyneins Kinesins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yogev Shaul
Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, Stanford, CA 94305, USA.
Cooper Roshni
Department of Electrical Engineering, Stanford University, 350 Serra Mall, Stanford, CA 94305, USA.
Fetter Richard
Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, Stanford, CA 94305, USA.
Horowitz Mark
Department of Electrical Engineering and Computer Science, Stanford University, 353 Serra Mall, Stanford, CA 94305, USA.
Shen Kang
Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, Stanford, CA 94305, USA. Electronic address: kangshen@stanford.edu.
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2016.09.036
Email
kangshen@stanford.edu
Published
2016-10-19
Pages
449-460
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC5432135
Subset
IM
Grants
NINDS NIH HHS · R01 NS034307 · United States
NINDS NIH HHS · R01 NS048392 · United States
NINDS NIH HHS · R01 NS082208 · United States
NINDS NIH HHS · R37 NS048392 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2016.09.036 PMC Full Text View journal details
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