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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 Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords CIN85; Dopamine receptor; Endocytosis; Hyperactivity; Synapse
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Journal EMBO Journal, The
Quellenangaben Volume: 29, Issue: 14, Pages: 2421-2432 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Heidelberg, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)