title: Microtubule Organization Determines Axonal Transport Dynamics.
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.
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, Stanford, CA 94305, USA.
authors.forename: Shaul
authors.initials: S
authors.lastname: Yogev
authors.affiliation: Department of Electrical Engineering, Stanford University, 350 Serra Mall, Stanford, CA 94305, USA.
authors.forename: Roshni
authors.initials: R
authors.lastname: Cooper
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, Stanford, CA 94305, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Fetter
authors.affiliation: Department of Electrical Engineering and Computer Science, Stanford University, 353 Serra Mall, Stanford, CA 94305, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, Stanford, CA 94305, USA. Electronic address: kangshen@stanford.edu.
authors.forename: Kang
authors.initials: K
authors.lastname: Shen
mesh_terms: D000818:Animals; D001370:Axonal Transport; D017173:Caenorhabditis elegans; D003599:Cytoskeleton / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D008853:Microscopy; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D011108:Polymers / Q000378:metabolism*; D015398:Signal Transduction; D059008:Time-Lapse Imaging
chemical_list: D008869:Microtubule-Associated Proteins; D011108:Polymers; D004398:Dyneins; D016547:Kinesins
keywords: C. elegans; axonal transport; dynein; kinesin; microtubule; microtubule dynamics; microtubule length; microtubule organization