Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2
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...
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| Veröffentlicht in: | The Journal of neuroscience 2005-02, Vol.25 (5), p.1219-1225 |
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| creator | Wang, Pei 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 |
| description | 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. |
| doi_str_mv | 10.1523/JNEUROSCI.4660-04.2005 |
| format | Article |
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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.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.4660-04.2005</identifier><identifier>PMID: 15689559</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Amyloid beta-Protein Precursor - deficiency ; Amyloid beta-Protein Precursor - genetics ; Amyloid beta-Protein Precursor - physiology ; Animals ; Animals, Newborn ; Biomarkers ; Diaphragm - chemistry ; Diaphragm - ultrastructure ; Mice ; Mice, Knockout ; Mice, Neurologic Mutants ; Motor Endplate - chemistry ; Motor Endplate - ultrastructure ; Muscle Proteins - chemistry ; Neck Muscles - chemistry ; Neck Muscles - ultrastructure ; Neurobiology of Disease ; Neuromuscular Junction - embryology ; Neuromuscular Junction - metabolism ; Phenotype ; Receptors, Cholinergic - chemistry ; Receptors, Presynaptic - chemistry ; Synaptic Transmission ; Synaptic Vesicles - chemistry</subject><ispartof>The Journal of neuroscience, 2005-02, Vol.25 (5), p.1219-1225</ispartof><rights>Copyright © 2005 Society for Neuroscience 0270-6474/05/251219-07.00/0 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-877cb93a8f45e6b5d8b534a0cf61e688561dd2326aa6d2da5bfda6d997f8ad683</citedby><cites>FETCH-LOGICAL-c593t-877cb93a8f45e6b5d8b534a0cf61e688561dd2326aa6d2da5bfda6d997f8ad683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6725967/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6725967/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15689559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Pei</creatorcontrib><creatorcontrib>Yang, Guang</creatorcontrib><creatorcontrib>Mosier, Dennis R</creatorcontrib><creatorcontrib>Chang, Paul</creatorcontrib><creatorcontrib>Zaidi, Tahire</creatorcontrib><creatorcontrib>Gong, Yan-Dao</creatorcontrib><creatorcontrib>Zhao, Nan-Ming</creatorcontrib><creatorcontrib>Dominguez, Bertha</creatorcontrib><creatorcontrib>Lee, Kuo-Fen</creatorcontrib><creatorcontrib>Gan, Wen-Biao</creatorcontrib><creatorcontrib>Zheng, Hui</creatorcontrib><title>Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>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.</description><subject>Amyloid beta-Protein Precursor - deficiency</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid beta-Protein Precursor - physiology</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Biomarkers</subject><subject>Diaphragm - chemistry</subject><subject>Diaphragm - ultrastructure</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, Neurologic Mutants</subject><subject>Motor Endplate - chemistry</subject><subject>Motor Endplate - ultrastructure</subject><subject>Muscle Proteins - chemistry</subject><subject>Neck Muscles - chemistry</subject><subject>Neck Muscles - ultrastructure</subject><subject>Neurobiology of Disease</subject><subject>Neuromuscular Junction - embryology</subject><subject>Neuromuscular Junction - metabolism</subject><subject>Phenotype</subject><subject>Receptors, Cholinergic - chemistry</subject><subject>Receptors, Presynaptic - chemistry</subject><subject>Synaptic Transmission</subject><subject>Synaptic Vesicles - chemistry</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvEzEUhS0EoqHwF6pZIbqY4MfYHm-QotBCUdpGlK4tj30nMZ1HsGca5d_jqFEKq658pPPdo3t9EDojeEo4ZZ9_3Fzc_7y9m19NCyFwjospxZi_QpPkqpwWmLxGE0wlzkUhixP0LsbfGGOJiXyLTggXpeJcTdDqK9RgB_8I2Q2MoW_HaMfGhOxu15lNhJj5Lrv2FrKFsQ--W2Wzdtf03mXLAHYMsQ9J9QMk7NNsuTzPTOeyJPKFf4CjRd-jN7VpInw4vKfo_vLi1_x7vrj9djWfLXLLFRvyUkpbKWbKuuAgKu7KirPCYFsLAqIsuSDOUUaFMcJRZ3hVu6SUknVpnCjZKfrylLsZqxachW4IptGb4FsTdro3Xv_vdH6tV_2jFpJyJWQK-HgICP2fEeKgWx8tNI3poB9j4pgSqsAvgkRylv6bJVA8gTb0MQaoj9sQrPdl6mOZel-mxoXel5kGz_695Xns0N7zCmu_Wm99AB1b0zQJJ3q73VKuuSaUKPYXK1-qVw</recordid><startdate>20050202</startdate><enddate>20050202</enddate><creator>Wang, Pei</creator><creator>Yang, Guang</creator><creator>Mosier, Dennis R</creator><creator>Chang, Paul</creator><creator>Zaidi, Tahire</creator><creator>Gong, Yan-Dao</creator><creator>Zhao, Nan-Ming</creator><creator>Dominguez, Bertha</creator><creator>Lee, Kuo-Fen</creator><creator>Gan, Wen-Biao</creator><creator>Zheng, Hui</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20050202</creationdate><title>Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2</title><author>Wang, Pei ; 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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-877cb93a8f45e6b5d8b534a0cf61e688561dd2326aa6d2da5bfda6d997f8ad683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Amyloid beta-Protein Precursor - deficiency</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid beta-Protein Precursor - physiology</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Biomarkers</topic><topic>Diaphragm - chemistry</topic><topic>Diaphragm - ultrastructure</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, Neurologic Mutants</topic><topic>Motor Endplate - chemistry</topic><topic>Motor Endplate - ultrastructure</topic><topic>Muscle Proteins - chemistry</topic><topic>Neck Muscles - chemistry</topic><topic>Neck Muscles - ultrastructure</topic><topic>Neurobiology of Disease</topic><topic>Neuromuscular Junction - embryology</topic><topic>Neuromuscular Junction - metabolism</topic><topic>Phenotype</topic><topic>Receptors, Cholinergic - chemistry</topic><topic>Receptors, Presynaptic - chemistry</topic><topic>Synaptic Transmission</topic><topic>Synaptic Vesicles - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Pei</creatorcontrib><creatorcontrib>Yang, Guang</creatorcontrib><creatorcontrib>Mosier, Dennis R</creatorcontrib><creatorcontrib>Chang, Paul</creatorcontrib><creatorcontrib>Zaidi, Tahire</creatorcontrib><creatorcontrib>Gong, Yan-Dao</creatorcontrib><creatorcontrib>Zhao, Nan-Ming</creatorcontrib><creatorcontrib>Dominguez, Bertha</creatorcontrib><creatorcontrib>Lee, Kuo-Fen</creatorcontrib><creatorcontrib>Gan, Wen-Biao</creatorcontrib><creatorcontrib>Zheng, Hui</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Pei</au><au>Yang, Guang</au><au>Mosier, Dennis R</au><au>Chang, Paul</au><au>Zaidi, Tahire</au><au>Gong, Yan-Dao</au><au>Zhao, Nan-Ming</au><au>Dominguez, Bertha</au><au>Lee, Kuo-Fen</au><au>Gan, Wen-Biao</au><au>Zheng, Hui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2005-02-02</date><risdate>2005</risdate><volume>25</volume><issue>5</issue><spage>1219</spage><epage>1225</epage><pages>1219-1225</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><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.</abstract><cop>United States</cop><pub>Soc Neuroscience</pub><pmid>15689559</pmid><doi>10.1523/JNEUROSCI.4660-04.2005</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Amyloid beta-Protein Precursor - deficiency Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - physiology Animals Animals, Newborn Biomarkers Diaphragm - chemistry Diaphragm - ultrastructure Mice Mice, Knockout Mice, Neurologic Mutants Motor Endplate - chemistry Motor Endplate - ultrastructure Muscle Proteins - chemistry Neck Muscles - chemistry Neck Muscles - ultrastructure Neurobiology of Disease Neuromuscular Junction - embryology Neuromuscular Junction - metabolism Phenotype Receptors, Cholinergic - chemistry Receptors, Presynaptic - chemistry Synaptic Transmission Synaptic Vesicles - chemistry |
| title | Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2 |
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