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  • Meyer, Sascha WDepartment of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)

APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP

  • Artikel/kapitelEngelska2011

Förlag, utgivningsår, omfång ...

  • 2011-04-26
  • Wiley,2011
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-373479
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-373479URI
  • https://doi.org/10.1038/emboj.2011.119DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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 och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Klevanski, MajaDepartment of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)
  • Delekate, AndreaCellular Neurobiology, Zoological Institute, TU Braunschweig, Braunschweig, Germany (författare)
  • Voikar, VooteleInstitute of Anatomy and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland (författare)
  • Aydin, DorotheeDepartment of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)
  • Hick, MeikeDepartment of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)
  • Filippov, MikhailDepartment of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)
  • Drost, NataliaDepartment of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)
  • Schaller, Kristin LDepartment of Cell and Developmental Biology, Institute of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO, USA (författare)
  • Sarr, MartinaDepartment of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)
  • Vogt, Miriam ADepartment for Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany (författare)
  • Gass, PeterDepartment of Biology, Institute of Human Movement Sciences, ETH Zurich, Zurich, Switzerland (författare)
  • Samanta, AyanUppsala universitet,Polymerkemi,Department of Pharmaceutical Chemistry, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany(Swepub:uu)ayasa773 (författare)
  • Jäschke, AndresDepartment of Pharmaceutical Chemistry, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)
  • Korte, MartinCellular Neurobiology, Zoological Institute, TU Braunschweig, Braunschweig, Germany (författare)
  • Wolfer, David PInstitute of Anatomy and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland (författare)
  • John H, CaldwellDepartment of Cell and Developmental Biology, Institute of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO, USA (författare)
  • Müller, Ulrike CDepartment of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany (författare)
  • Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, GermanyCellular Neurobiology, Zoological Institute, TU Braunschweig, Braunschweig, Germany (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:European Molecular Biology Organization: Wiley30, s. 2266-22801460-2075
  • Ingår i:The EMBO Journal: Wiley30, s. 2266-22800261-4189

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