Amyloid precursor protein at node of Ranvier modulates nodal formation
Identifieur interne : 002080 ( Ncbi/Curation ); précédent : 002079; suivant : 002081Amyloid precursor protein at node of Ranvier modulates nodal formation
Auteurs : De-En Xu [République populaire de Chine] ; Wen-Min Zhang [République populaire de Chine] ; Zara Zhuyun Yang [République populaire de Chine, Australie] ; Hong-Mei Zhu [République populaire de Chine, Australie] ; Ke Yan [République populaire de Chine] ; Shao Li [République populaire de Chine] ; Dominique Bagnard [France] ; Gavin S. Dawe [Singapour] ; Quan-Hong Ma [République populaire de Chine] ; Zhi-Cheng Xiao [République populaire de Chine, Australie]Source :
- Cell Adhesion & Migration [ 1933-6918 ] ; 2014.
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.
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DOI: 10.4161/cam.28802
PubMed: 25482638
PubMed Central: 4594432
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Institute of Neuroscience; the Second Affiliated Hospital; Soochow University</institution>; Suzhou,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Wen Min" sort="Zhang, Wen Min" uniqKey="Zhang W" first="Wen-Min" last="Zhang">Wen-Min Zhang</name><affiliation wicri:level="1"><nlm:aff id="af0001"><institution>Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases; Institute of Neuroscience; the Second Affiliated Hospital; Soochow University</institution>; Suzhou,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Zara Zhuyun" sort="Yang, Zara Zhuyun" uniqKey="Yang Z" first="Zara Zhuyun" last="Yang">Zara Zhuyun Yang</name><affiliation wicri:level="1"><nlm:aff id="af0002"><institution>The Key Laboratory of Stem Cell and Regenerative Medicine; Institute of Molecular and Clinical Medicine; Kunming Medical College</institution>; Kunming,<country>PR China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University</institution>; Clayton, Melbourne,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhu, Hong Mei" sort="Zhu, Hong Mei" uniqKey="Zhu H" first="Hong-Mei" last="Zhu">Hong-Mei Zhu</name><affiliation wicri:level="1"><nlm:aff id="af0002"><institution>The Key Laboratory of Stem Cell and Regenerative Medicine; Institute of Molecular and Clinical Medicine; Kunming Medical College</institution>; Kunming,<country>PR China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University</institution>; Clayton, Melbourne,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yan, Ke" sort="Yan, Ke" uniqKey="Yan K" first="Ke" last="Yan">Ke Yan</name><affiliation wicri:level="1"><nlm:aff id="af0001"><institution>Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases; Institute of Neuroscience; the Second Affiliated Hospital; Soochow University</institution>; Suzhou,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Shao" sort="Li, Shao" uniqKey="Li S" first="Shao" last="Li">Shao Li</name><affiliation wicri:level="1"><nlm:aff id="af0002"><institution>The Key Laboratory of Stem Cell and Regenerative Medicine; Institute of Molecular and Clinical Medicine; Kunming Medical College</institution>; Kunming,<country>PR China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0004"><institution>Department of Physiology; Dalian Medical University</institution>; Dalian,<country>PR China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bagnard, Dominique" sort="Bagnard, Dominique" uniqKey="Bagnard D" first="Dominique" last="Bagnard">Dominique Bagnard</name><affiliation wicri:level="1"><nlm:aff id="af0005"><institution>INSERM U682; University of Strasbourg</institution>; Strasbourg,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dawe, Gavin S" sort="Dawe, Gavin S" uniqKey="Dawe G" first="Gavin S" last="Dawe">Gavin S. Dawe</name><affiliation wicri:level="1"><nlm:aff id="af0006"><institution>SINAPSE; Singapore Institute for Neurotechnology</institution>;<country>Singapore</country></nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0007"><institution>Department of Pharmacology; Yong Loo Lin School of Medicine; National University Health System; National University of Singapore</institution>;<country>Singapore</country></nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0008"><institution>Neurobiology and Ageing Programme; Life Sciences Institute; National University of Singapore</institution>;<country>Singapore</country></nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ma, Quan Hong" sort="Ma, Quan Hong" uniqKey="Ma Q" first="Quan-Hong" last="Ma">Quan-Hong Ma</name><affiliation wicri:level="1"><nlm:aff id="af0001"><institution>Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases; Institute of Neuroscience; the Second Affiliated Hospital; Soochow University</institution>; Suzhou,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Xiao, Zhi Cheng" sort="Xiao, Zhi Cheng" uniqKey="Xiao Z" first="Zhi-Cheng" last="Xiao">Zhi-Cheng Xiao</name><affiliation wicri:level="1"><nlm:aff id="af0002"><institution>The Key Laboratory of Stem Cell and Regenerative Medicine; Institute of Molecular and Clinical Medicine; Kunming Medical College</institution>; Kunming,<country>PR China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af0003"><institution>Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University</institution>; Clayton, Melbourne,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cell Adhesion & Migration</title><idno type="ISSN">1933-6918</idno><idno type="eISSN">1933-6926</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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