Developmental mechanism of the periodic membrane skeleton in axons

  1. Guisheng Zhong
  2. Jiang He
  3. Ruobo Zhou
  4. Damaris Lorenzo
  5. Hazen P Babcock
  6. Vann Bennett
  7. Xiaowei Zhuang  Is a corresponding author
  1. Howard Hughes Medical Institute, Harvard University, United States
  2. Duke University, United States
  3. Harvard University, United States
  4. Howard Hughes Medical Institute, Duke University, United States

Abstract

Actin, spectrin and associated molecules form a periodic sub-membrane lattice structure in axons. How this membrane skeleton is developed and why it preferentially forms in axons are unknown. Here, we studied the developmental mechanism of this lattice structure. We found that this structure emerged early during axon development and propagated from proximal regions to distal ends of axons. Components of the axon initial segment were recruited to the lattice late during development. Formation of the lattice was regulated by the local concentration of βII spectrin, which is higher in axons than in dendrites. Increasing the dendritic concentration of βII spectrin by over-expression or by knocking out ankyrin B induced the formation of the periodic structure in dendrites, demonstrating that the spectrin concentration is a key determinant in the preferential development of this structure in axons and that ankyrin B is critical for the polarized distribution of βII spectrin in neurites.

Article and author information

Author details

  1. Guisheng Zhong

    Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  2. Jiang He

    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  3. Ruobo Zhou

    Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Damaris Lorenzo

    Department of Biochemistry, Duke University, Durham, United States
    Competing interests
    No competing interests declared.
  5. Hazen P Babcock

    Center for Brain Sciences, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  6. Vann Bennett

    Department of Biochemistry and Department of Neurobiology, Howard Hughes Medical Institute, Duke University, Durham, United States
    Competing interests
    No competing interests declared.
  7. Xiaowei Zhuang

    Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    For correspondence
    zhuang@chemistry.harvard.edu
    Competing interests
    Xiaowei Zhuang, Reviewing editor, eLife.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol, number 10-16. The protocol was approved by the Committee on the Use of Animals in Research and Teaching of Harvard University Faculty of Arts & Sciences (HU/FAS). The HU/FAS animal care and use program is AAALAC International accredited, has a PHS Assurance (A3593-01) on file with NIH's Office of Laboratory Animal Welfare, and is registered with the USDA (14-R-0128). Animals were euthanized in accordance with AVMA Guidelines for the Euthanasia of Animals

Reviewing Editor

  1. Robert H Singer, Albert Einstein College of Medicine, United States

Publication history

  1. Received: September 2, 2014
  2. Accepted: December 18, 2014
  3. Accepted Manuscript published: December 23, 2014 (version 1)
  4. Version of Record published: February 6, 2015 (version 2)

Copyright

© 2014, Zhong 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. Guisheng Zhong
  2. Jiang He
  3. Ruobo Zhou
  4. Damaris Lorenzo
  5. Hazen P Babcock
  6. Vann Bennett
  7. Xiaowei Zhuang
(2014)
Developmental mechanism of the periodic membrane skeleton in axons
eLife 3:e04581.
https://doi.org/10.7554/eLife.04581

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