1. Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2
- Author
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Wen-Biao Gan, Dennis R. Mosier, Tahire Zaidi, Bertha Dominguez, Kuo-Fen Lee, Yan Dao Gong, Paul C. Chang, Nan Ming Zhao, Guang Yang, Hui Zheng, and Pei Wang
- Subjects
Diaphragm ,Neuromuscular Junction ,Muscle Proteins ,Neurotransmission ,Biology ,Receptors, Presynaptic ,Synaptic vesicle ,Motor Endplate ,Synaptic Transmission ,Neuromuscular junction ,chemistry.chemical_compound ,Amyloid beta-Protein Precursor ,Mice ,Mice, Neurologic Mutants ,Neck Muscles ,Neurobiology of Disease ,mental disorders ,medicine ,Amyloid precursor protein ,Animals ,Receptors, Cholinergic ,APLP1 ,Neurotransmitter ,Acetylcholine receptor ,Mice, Knockout ,General Neuroscience ,P3 peptide ,medicine.anatomical_structure ,Phenotype ,chemistry ,Animals, Newborn ,biology.protein ,Synaptic Vesicles ,Neuroscience ,Biomarkers - Abstract
Biochemical and genetic studies place the amyloid precursor protein (APP) at the center stage of Alzheimer's disease (AD) pathogenesis. Although mutations in theAPPgene lead to dominant inheritance of familial AD, the normal function of APP remains elusive. Here, we report that the APP family of proteins plays an essential role in the development of neuromuscular synapses. Mice deficient inAPPand its homolog APP-like protein 2 (APLP2) exhibit aberrant apposition of presynaptic marker proteins with postsynaptic acetylcholine receptors and excessive nerve terminal sprouting. The number of synaptic vesicles at presynaptic terminals is dramatically reduced. These structural abnormalities are accompanied by defective neurotransmitter release and a high incidence of synaptic failure. Our results identify APP/APLP2 as key regulators of structure and function of developing neuromuscular synapses.
- Published
- 2005