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  • Shimokawa, NoriakiInstitute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany (author)

CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice

  • Article/chapterEnglish2010

Publisher, publication year, extent ...

  • 2010-06-15
  • European Molecular Biology Organization,2010
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-131272
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-131272URI
  • https://doi.org/10.1038/emboj.2010.120DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-46256URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:121017319URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Despite extensive investigations of Cbl-interacting protein of 85 kDa (CIN85) in receptor trafficking and cytoskeletal dynamics, little is known about its functions in vivo. Here, we report the study of a mouse deficient of the two CIN85 isoforms expressed in the central nervous system, exposing a function of CIN85 in dopamine receptor endocytosis. Mice lacking CIN85 exon 2 (CIN85(Deltaex2)) show hyperactivity phenotypes, characterized by increased physical activity and exploratory behaviour. Interestingly, CIN85(Deltaex2) animals display abnormally high levels of dopamine and D2 dopamine receptors (D2DRs) in the striatum, an important centre for the coordination of animal behaviour. Importantly, CIN85 localizes to the post-synaptic compartment of striatal neurons in which it co-clusters with D2DRs. Moreover, it interacts with endocytic regulators such as dynamin and endophilins in the striatum. Absence of striatal CIN85 causes insufficient complex formation of endophilins with D2DRs in the striatum and ultimately decreased D2DR endocytosis in striatal neurons in response to dopamine stimulation. These findings indicate an important function of CIN85 in the regulation of dopamine receptor functions and provide a molecular explanation for the hyperactive behaviour of CIN85(Deltaex2) mice.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Haglund, KaisaInstitute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany (author)
  • Hölter, Sabine MInstitute of Developmental Genetics, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Neuherberg, Germany (author)
  • Grabbe, CarolineInstitute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany(Swepub:umu)caegre98 (author)
  • Kirkin, VladimirInstitute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany (author)
  • Koibuchi, NoriyukiDepartment of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma, Japan (author)
  • Schultz, ChristianInstitute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Frankfurt (Main), Germany (author)
  • Rozman, JanMolecular Nutritional Medicine, Else-Kroner-Fresenius Center, Technische Universitat Munchen, Freising-Weihenstephan, Germany (author)
  • Hoeller, DanielaInstitute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany (author)
  • Qiu, Chun-HongDepartment of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma, Japan (author)
  • Londoño, Marina BDepartment of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma, Japan (author)
  • Ikezawa, JunDepartment of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma, Japan (author)
  • Jedlicka, PeterInstitute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Frankfurt (Main), Germany (author)
  • Stein, BirgitInstitute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany (author)
  • Schwarzacher, Stephan WInstitute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Frankfurt (Main), Germany,Institute of Developmental Genetics, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Neuherberg, Germany (author)
  • Wolfer, David PInstitute of Anatomy, University of Zurich, and Institute of Human Movement Sciences and Sport, ETH Zurich, Zurich, Switzerland (author)
  • Ehrhardt, NicoleMolecular Nutritional Medicine, Else-Kroner-Fresenius Center, Technische Universitat Munchen, Freising-Weihenstephan, Germany (author)
  • Heuchel, RainerKarolinska Institutet,Uppsala universitet,Ludwiginstitutet för cancerforskning(Swepub:uu)rainheuc (author)
  • Nezis, IoannisDepartment of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway (author)
  • Brech, AndreasDepartment of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway (author)
  • Schmidt, Mirko H HInstitute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany (author)
  • Fuchs, HelmutInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany (author)
  • Gailus-Durner, ValerieInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany (author)
  • Klingenspor, MartinMolecular Nutritional Medicine, Else-Kroner-Fresenius Center, Technische Universitat Munchen, Freising-Weihenstephan, Germany (author)
  • Bogler, OliverDepartments of Neurosurgery, Neuro-Oncology and Brain Tumor Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA (author)
  • Wurst, WolfgangInstitute of Developmental Genetics, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Neuherberg, Germany (author)
  • Deller, ThomasInstitute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Frankfurt (Main), Germany (author)
  • de Angelis, Martin HrabéInstitute of Experimental Genetics and German Mouse Clinic, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany (author)
  • Dikic, IvanInstitute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany (author)
  • Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), GermanyInstitute of Developmental Genetics, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Neuherberg, Germany (creator_code:org_t)

Related titles

  • In:EMBO Journal: European Molecular Biology Organization29:14, s. 2421-24320261-41891460-2075

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