title: Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2.
abstract: Biochemical and genetic studies place the amyloid precursor protein (APP) at the center stage of Alzheimer's disease (AD) pathogenesis. Although mutations in the APP gene 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 in APP and 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.
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Mosier
authors.forename: Paul
authors.initials: P
authors.lastname: Chang
authors.forename: Tahire
authors.initials: T
authors.lastname: Zaidi
authors.forename: Yan-Dao
authors.initials: YD
authors.lastname: Gong
authors.forename: Nan-Ming
authors.initials: NM
authors.lastname: Zhao
authors.forename: Bertha
authors.initials: B
authors.lastname: Dominguez
authors.forename: Kuo-Fen
authors.initials: KF
authors.lastname: Lee
authors.forename: Wen-Biao
authors.initials: WB
authors.lastname: Gan
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D003964:Diaphragm / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009045:Motor Endplate / Q000737:chemistry / Q000648:ultrastructure; D009124:Muscle Proteins / Q000737:chemistry; D009334:Neck Muscles / Q000737:chemistry / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000196:embryology / Q000378:metabolism*; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000737:chemistry; D017661:Receptors, Presynaptic / Q000737:chemistry; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000737:chemistry
chemical_list: D016564:Amyloid beta-Protein Precursor; C492952:Aplp2 protein, mouse; D015415:Biomarkers; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D017661:Receptors, Presynaptic