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APP and APLP2 are e...
APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP
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- Meyer, Sascha W (författare)
- Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Klevanski, Maja (författare)
- Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Delekate, Andrea (författare)
- Cellular Neurobiology, Zoological Institute, TU Braunschweig, Braunschweig, Germany
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- Voikar, Vootele (författare)
- Institute of Anatomy and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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- Aydin, Dorothee (författare)
- Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Hick, Meike (författare)
- Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Filippov, Mikhail (författare)
- Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Drost, Natalia (författare)
- Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Schaller, Kristin L (författare)
- Department of Cell and Developmental Biology, Institute of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO, USA
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- Sarr, Martina (författare)
- Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Vogt, Miriam A (författare)
- Department for Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany
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- Gass, Peter (författare)
- Department of Biology, Institute of Human Movement Sciences, ETH Zurich, Zurich, Switzerland
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- Samanta, Ayan (författare)
- Uppsala universitet,Polymerkemi,Department of Pharmaceutical Chemistry, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Jäschke, Andres (författare)
- Department of Pharmaceutical Chemistry, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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- Korte, Martin (författare)
- Cellular Neurobiology, Zoological Institute, TU Braunschweig, Braunschweig, Germany
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- Wolfer, David P (författare)
- Institute of Anatomy and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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- John H, Caldwell (författare)
- Department of Cell and Developmental Biology, Institute of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO, USA
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- Müller, Ulrike C (författare)
- Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
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(creator_code:org_t)
- 2011-04-26
- 2011
- Engelska.
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Ingår i: European Molecular Biology Organization. - : Wiley. - 1460-2075. ; 30, s. 2266-2280
- Relaterad länk:
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https://doi.org/10.1...
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http://emboj.embopre...
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https://uu.diva-port... (primary) (Raw object)
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Despite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and its proteolytic fragments are still poorly understood. Previously, we generated APPsα knock‐in (KI) mice expressing solely the secreted ectodomain APPsα. Here, we generated double mutants (APPsα‐DM) by crossing APPsα‐KI mice onto an APLP2‐deficient background and show that APPsα rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice. Surviving APPsα‐DM mice exhibited impaired neuromuscular transmission, with reductions in quantal content, readily releasable pool, and ability to sustain vesicle release that resulted in muscular weakness. We show that these defects may be due to loss of an APP/Mint2/Munc18 complex. Moreover, APPsα‐DM muscle showed fragmented post‐synaptic specializations, suggesting impaired postnatal synaptic maturation and/or maintenance. Despite normal CNS morphology and unaltered basal synaptic transmission, young APPsα‐DM mice already showed pronounced hippocampal dysfunction, impaired spatial learning and a deficit in LTP that could be rescued by GABAA receptor inhibition. Collectively, our data show that APLP2 and APP are synergistically required to mediate neuromuscular transmission, spatial learning and synaptic plasticity.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Alzheimer; amyloid precursor protein; knockout; learning; synaptic plasticity
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Meyer, Sascha W
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Klevanski, Maja
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Delekate, Andrea
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Voikar, Vootele
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Aydin, Dorothee
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Hick, Meike
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visa fler...
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Filippov, Mikhai ...
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Drost, Natalia
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Schaller, Kristi ...
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Sarr, Martina
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Vogt, Miriam A
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Gass, Peter
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Samanta, Ayan
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Jäschke, Andres
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Korte, Martin
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Wolfer, David P
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John H, Caldwell
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Müller, Ulrike C
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visa färre...
- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Biokemi och mole ...
- Artiklar i publikationen
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European Molecul ...
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The EMBO Journal
- Av lärosätet
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Uppsala universitet