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PMID: 15689559 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 25 ·No. 5 ·2005-02-02 ·Pages 1219-25

Wang P, Yang G, Mosier DR, Chang P, Zaidi T, Gong YD, Zhao NM, Dominguez B, Lee KF, Gan WB, Zheng H

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.

MeSH Terms
Amyloid beta-Protein Precursor/deficiency,genetics,physiology Animals Animals, Newborn Biomarkers Diaphragm/chemistry,ultrastructure Mice Mice, Knockout Mice, Neurologic Mutants Motor Endplate/chemistry,ultrastructure Muscle Proteins/chemistry Neck Muscles/chemistry,ultrastructure Neuromuscular Junction/embryology,metabolism Phenotype Receptors, Cholinergic/chemistry Receptors, Presynaptic/chemistry Synaptic Transmission Synaptic Vesicles/chemistry
Chemicals
Amyloid beta-Protein Precursor Aplp2 protein, mouse Biomarkers Muscle Proteins Receptors, Cholinergic Receptors, Presynaptic
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Wang Pei
Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA.
Yang Guang
Mosier Dennis R
Chang Paul
Zaidi Tahire
Gong Yan-Dao
Zhao Nan-Ming
Dominguez Bertha
Lee Kuo-Fen
Gan Wen-Biao
Zheng Hui
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4660-04.2005
Published
2005-02-02
Pages
1219-25
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6725967
Subset
IM
Grants
NINDS NIH HHS · NS041846 · United States
NINDS NIH HHS · R01 NS041846 · United States
NIA NIH HHS · R01 AG021141 · United States
NINDS NIH HHS · NS40039 · United States
NINDS NIH HHS · R01 NS040039 · United States
NIA NIH HHS · AG20670 · United States
NIA NIH HHS · R01 AG020670 · United States
NIA NIH HHS · AG21141 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.4660-04.2005 PMC Full Text View journal details
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