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Shimokawa, N.* ; Haglund, K.* ; Hölter, S.M. ; Grabbe, C.* ; Kirkin, V.* ; Koibuchi, N.* ; Schultz, C.* ; Rozman, J. ; Hoeller, D.* ; Qiu, C.H.* ; Londono, M.B.* ; Ikezawa, J.* ; Jedlicka, P.* ; Stein, B.* ; Schwarzacher, S.W.* ; Wolfer, D.P.* ; Ehrhardt, N. ; Heuchel, R.* ; Nezis, I.* ; Brech, A.* ; Schmidt, M.H.H.* ; Fuchs, H. ; Gailus-Durner, V. ; Klingenspor, M.* ; Bogler, O.* ; Wurst, W. ; Deller, T.* ; Hrabě de Angelis, M. ; Dikic, I.*

CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice.

EMBO J. 29, 2421-2432 (2010)
DOI PMC
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter CIN85; Dopamine receptor; Endocytosis; Hyperactivity; Synapse
Sprache englisch
Veröffentlichungsjahr 2010
HGF-Berichtsjahr 2010
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Quellenangaben Band: 29, Heft: 14, Seiten: 2421-2432 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Heidelberg, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
POF Topic(s) 30201 - Metabolic Health
30204 - Cell Programming and Repair
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500600-003
G-500600-001
G-500500-001
PubMed ID 20551902
DOI 10.1038/emboj.2010.120
Scopus ID 77954886631
Erfassungsdatum 2010-07-29
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