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Abstract
Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
This work was supported by grants from The Talent Program of Yunnan Province, China, and The Professorial Fellowship of Monash University, Australia, to ZC Xiao from the National Basic Research Program of China (973 program) (2013CB945602), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, Suzhou Science and Technology Development Program (SZS201205), and the National Natural Science Foundation of China (31171313 and 81271424), to QH Ma from MERLION, a Singapore-France joint scientific program, to both ZC Xiao and D Bagnard; and from the National Medical Research Council of Singapore (NMRC/1059/2006) to both GS Dawe and ZC Xiao. We are grateful to Prof Dennis Selkoe (Harvard University) for generously providing APP antibodies and to Dr Hasan Mohajeri (University of Zurich) for preparing the samples of APP transgenic mice.
Supplemental Material
Supplemental material may be found here: www.landesbioscience.com/journals/celladhesion/article/28802.