Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain.
The mechanisms regulating the outgrowth of neurites during development, as well as after injury, are key to the understanding of the wiring and functioning of the brain under normal and pathological conditions. The amyloid precursor protein (APP) is involved in the pathogenesis of Alzheimer's disease (AD). However, its physiological role in the central nervous system is not known. Many physical interactions between APP and intracellular signalling molecules have been described, but their functional relevance remains unclear. We show here that human APP and Drosophila APP-Like (APPL) can induce postdevelopmental axonal arborization, which depends critically on a conserved motif in the C-terminus and requires interaction with the Abelson (Abl) tyrosine kinase. Brain injury induces APPL upregulation in Drosophila neurons, correlating with increased post-traumatic mortality in appl(d) mutant flies. Finally, we also found interactions between APP and the JNK stress kinase cascade. Our findings suggest a role for APP in axonal outgrowth after traumatic brain injury.
Leyssen
Maarten
M
Laboratory of Neurogenetics, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB) and University of Leuven, School of Medicine, Leuven, Belgium.
Ayaz
Derya
D
Hébert
Sébastien S
SS
Reeve
Simon
S
De Strooper
Bart
B
Hassan
Bassem A
BA
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism* / Q000502:physiology; D058255:Protease Nexins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013696:Temperature
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C066839:Appl protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; C506548:Abl protein, Drosophila; D048670:MAP Kinase Kinase 4