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Updated: May 18, 2026

Ex Vivo Imaging of Postnatal Cerebellar Granule Cell Migration Using Confocal Macroscopy
Published on: May 12, 2015
Pancortins interact with amyloid precursor protein and modulate cortical cell migration
Heather C Rice1, Matthew Townsend, Jilin Bai
1Center for Neurologic Diseases, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Amyloid precursor protein (APP) interacts with pancortins, influencing neuronal precursor cell migration during brain development. Different pancortin isoforms have opposing roles, highlighting their combined function with APP in cortical development.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Neuronal precursor cell migration is crucial for mammalian brain development.
- Amyloid precursor protein (APP) interacts with cytosolic proteins (DAB1, DISC1) to regulate migration.
- Extracellular factors signaling through APP are key to understanding migration regulation.
Purpose of the Study:
- To identify extracellular factors interacting with APP that regulate neuronal migration.
- To investigate the biochemical and functional relationship between APP and pancortins during cortical development.
Main Methods:
- Unbiased mass spectrometry screen to identify APP-binding proteins.
- Co-immunoprecipitation to confirm APP-pancortin interactions.
- In utero electroporation for pancortin gain and loss-of-function studies.
- Cell culture experiments to assess APP cleavage.
Main Results:
- Identified pancortins as novel APP-binding partners in the rodent brain.
- Demonstrated interaction of APP with all four mammalian pancortin isoforms (AMY, AMZ, BMY, BMZ).
- Showed that BMZ and BMY pancortins reduce APP cleavage by β-secretase.
- Revealed opposing roles for pancortin isoforms in neuronal migration into the cortical plate.
- Established that pancortins and APP function together to regulate cortical entry.
Conclusions:
- Pancortins biochemically and functionally interact with APP.
- Pancortins play a previously unrecognized role in mammalian cortical development.
- The APP-pancortin complex is essential for proper neuronal precursor cell migration.
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