1. Neuroscience

Dynamic proteomic and phosphoproteomic atlas of corticostriatal axons in neurodevelopment

  1. Vasin Dumrongprechachan
  2. Ryan B Salisbury
  3. Lindsey Butler
  4. Matthew L MacDonald  Is a corresponding author
  5. Yevgenia Kozorovitskiy  Is a corresponding author
  1. Northwestern University, United States
  2. University of Pittsburgh, United States
https://doi.org/10.7554/eLife.78847
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  1. Vasin Dumrongprechachan
  2. Ryan B Salisbury
  3. Lindsey Butler
  4. Matthew L MacDonald
  5. Yevgenia Kozorovitskiy
(2022)
Dynamic proteomic and phosphoproteomic atlas of corticostriatal axons in neurodevelopment
eLife 11:e78847.
https://doi.org/10.7554/eLife.78847
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Abstract

Mammalian axonal development begins in embryonic stages and continues postnatally. After birth, axonal proteomic landscape changes rapidly, coordinated by transcription, protein turnover, and post-translational modifications. Comprehensive profiling of axonal proteomes across neurodevelopment is limited, with most studies lacking cell-type and neural circuit specificity, resulting in substantial information loss. We create a Cre-dependent APEX2 reporter mouse line and map cell-type specific proteome of corticostriatal projections across postnatal development. We synthesize analysis frameworks to define temporal patterns of axonal proteome and phosphoproteome, identifying co-regulated proteins and phosphorylations associated with genetic risk for human brain disorders. We discover proline-directed kinases as major developmental regulators. APEX2 transgenic reporter proximity labeling offers flexible strategies for subcellular proteomics with cell type specificity in early neurodevelopment, a critical period for neuropsychiatric disease.

Data availability

Mass spectrometry raw data have been deposited in the PRIDE database (accession number: PXD030864. Code is available at Github (link in Materials and Methods). All analyzed proteomics results are also included as supplementary files. All uncropped gels and blots are included as source data.

The following data sets were generated

Article and author information

Author details

  1. Vasin Dumrongprechachan

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5890-6778

  2. Ryan B Salisbury

    Department of Psychiatry, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Lindsey Butler

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Matthew L MacDonald

    Department of Psychiatry, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    macdonaldml@upmc.edu
    Competing interests
    The authors declare that no competing interests exist.

  5. Yevgenia Kozorovitskiy

    Department of Neurobiology, Northwestern University, Evanston, United States
    For correspondence
    Yevgenia.Kozorovitskiy@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3710-1484

Funding

National Institute of Mental Health (R56MH113923)

  • Yevgenia Kozorovitskiy

American Heart Association (19PRE34380056)

  • Vasin Dumrongprechachan

National Institute of General Medical Sciences (2T32GM15538)

  • Vasin Dumrongprechachan

National Institute of Neurological Disorders and Stroke (R01NS107539)

  • Yevgenia Kozorovitskiy

National Institute of Mental Health (R01MH117111)

  • Yevgenia Kozorovitskiy

National Science Foundation (1846234)

  • Yevgenia Kozorovitskiy

Arnold and Mabel Beckman Foundation (Beckman Young Investigator Award)

  • Yevgenia Kozorovitskiy

Kinship Foundation (Searle Scholar Award)

  • Yevgenia Kozorovitskiy

Rita Allen Foundation (Rita Allen Foundation Scholar Award)

  • Yevgenia Kozorovitskiy

Alfred P. Sloan Foundation (Sloan Research Fellowship)

  • Yevgenia Kozorovitskiy

National Institute of Mental Health (R01MH118497)

  • Matthew L MacDonald

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

Reviewing Editor

  1. Nils Brose, Max Planck Institute of Experimental Medicine, Germany

Ethics

Animal experimentation: Animals were handled according to protocols approved by the Northwestern University AnimalCare and Use Committee. (protocol number: IS00008060).

Version history

  1. Preprint posted: March 22, 2022 (view preprint)
  2. Received: March 22, 2022
  3. Accepted: October 12, 2022
  4. Accepted Manuscript published: October 14, 2022 (version 1)
  5. Version of Record published: November 2, 2022 (version 2)

Copyright

© 2022, Dumrongprechachan 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. Vasin Dumrongprechachan
  2. Ryan B Salisbury
  3. Lindsey Butler
  4. Matthew L MacDonald
  5. Yevgenia Kozorovitskiy
(2022)
Dynamic proteomic and phosphoproteomic atlas of corticostriatal axons in neurodevelopment
eLife 11:e78847.
https://doi.org/10.7554/eLife.78847

Share this article

https://doi.org/10.7554/eLife.78847

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