Dynamic proteomic and phosphoproteomic atlas of corticostriatal axons in neurodevelopment
- Northwestern University, United States
- 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.
Article and author information
Author details
Vasin Dumrongprechachan
Yevgenia Kozorovitskiy
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.
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Dynamic proteomic and phosphoproteomic atlas of corticostriatal axons in neurodevelopment
eLife 11:e78847.
https://doi.org/10.7554/eLife.78847
