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

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.

Ethics

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

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.

Metrics

  • 2,490
    views
  • 379
    downloads
  • 10
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Neuroscience
    Sven Ohl, Martin Rolfs
    Research Article

    Detecting causal relations structures our perception of events in the world. Here, we determined for visual interactions whether generalized (i.e. feature-invariant) or specialized (i.e. feature-selective) visual routines underlie the perception of causality. To this end, we applied a visual adaptation protocol to assess the adaptability of specific features in classical launching events of simple geometric shapes. We asked observers to report whether they observed a launch or a pass in ambiguous test events (i.e. the overlap between two discs varied from trial to trial). After prolonged exposure to causal launch events (the adaptor) defined by a particular set of features (i.e. a particular motion direction, motion speed, or feature conjunction), observers were less likely to see causal launches in subsequent ambiguous test events than before adaptation. Crucially, adaptation was contingent on the causal impression in launches as demonstrated by a lack of adaptation in non-causal control events. We assessed whether this negative aftereffect transfers to test events with a new set of feature values that were not presented during adaptation. Processing in specialized (as opposed to generalized) visual routines predicts that the transfer of visual adaptation depends on the feature similarity of the adaptor and the test event. We show that the negative aftereffects do not transfer to unadapted launch directions but do transfer to launch events of different speeds. Finally, we used colored discs to assign distinct feature-based identities to the launching and the launched stimulus. We found that the adaptation transferred across colors if the test event had the same motion direction as the adaptor. In summary, visual adaptation allowed us to carve out a visual feature space underlying the perception of causality and revealed specialized visual routines that are tuned to a launch’s motion direction.

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.