MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport

  1. Stephen R Tymanskyj
  2. Benjamin H Yang
  3. Kristen J Verhey
  4. Le Ma  Is a corresponding author
  1. Thomas Jefferson University, United States
  2. University of Michigan Medical School, United States

Abstract

Neuronal cell morphogenesis depends on the proper regulation of microtubule-based transport, but the underlying mechanisms are not well understood. Here, we report our study of MAP7, a unique microtubule-associated protein that interacts with both microtubules and the motor protein kinesin-1. Structure-function analysis in rat embryonic sensory neurons shows that the kinesin-1 interacting domain in MAP7 is required for axon and branch growth but not for branch formation. Also, two unique microtubule binding sites are found in MAP7 that have distinct dissociation kinetics and are both required for branch formation. Furthermore, MAP7 recruits kinesin-1 dynamically to microtubules, leading to alterations in organelle transport behaviors, particularly pause/speed switching frequency. As MAP7 is localized to branch sites, our results suggest a novel mechanism mediated by the dual interactions between MAP7 with microtubules and kinesin-1 in the precise control of microtubule-based transport during axon morphogenesis.

Data availability

All quantitative data for statistical analysis shown in figures are provided as source data in corresponding Excel sheets.

Article and author information

Author details

  1. Stephen R Tymanskyj

    Department of Neuroscience, Thomas Jefferson University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Benjamin H Yang

    Department of Neuroscience, Thomas Jefferson University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kristen J Verhey

    Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9329-4981
  4. Le Ma

    Department of Neuroscience, Thomas Jefferson University, Philadelphia, United States
    For correspondence
    le.ma@jefferson.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2769-9416

Funding

National Institute of Neurological Disorders and Stroke (NS062047)

  • Le Ma

Pennsylvania Department of Health (SAP # 4100068728)

  • Le Ma

National Institute of General Medical Sciences (GM070862)

  • Kristen J Verhey

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The study was performed in strict accordance with the Guidelines for the Care and Use of Laboratory Animals of the National Institutes of Health and the approved IACUC protocol (#01560) of the Thomas Jefferson University.

Reviewing Editor

  1. Kang Shen, Stanford University, United States

Publication history

  1. Received: March 5, 2018
  2. Accepted: August 21, 2018
  3. Accepted Manuscript published: August 22, 2018 (version 1)
  4. Version of Record published: September 11, 2018 (version 2)

Copyright

© 2018, Tymanskyj et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Stephen R Tymanskyj
  2. Benjamin H Yang
  3. Kristen J Verhey
  4. Le Ma
(2018)
MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport
eLife 7:e36374.
https://doi.org/10.7554/eLife.36374

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