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CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice
Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany.
Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany.
Institute of Developmental Genetics, Helmholtz Zentrum Mu¨nchen, German Research Center for Environmental Health, Neuherberg, Germany.
Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Frankfurt (Main), Germany.
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2010 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 29, no 14, 2421-2432 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
European Molecular Biology Organization , 2010. Vol. 29, no 14, 2421-2432 p.
Keyword [en]
CIN85, dopamine receptor, endocytosis hyperactivity, synapse
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-131272DOI: 10.1038/emboj.2010.120ISI: 000280148500016PubMedID: 20551902OAI: oai:DiVA.org:uu-131272DiVA: diva2:353898
Available from: 2010-09-29 Created: 2010-09-29 Last updated: 2017-12-12Bibliographically approved

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