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CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice
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(2010) CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice. The EMBO Journal, Vol. 29 (No. 14). pp. 2421-2432. doi:10.1038/emboj.2010.120 ISSN 0261-4189.
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Official URL: http://dx.doi.org/10.1038/emboj.2010.120
Abstract
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.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | The EMBO Journal | ||||
Publisher: | Nature Publishing Group | ||||
ISSN: | 0261-4189 | ||||
Official Date: | 2010 | ||||
Dates: |
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Volume: | Vol. 29 | ||||
Number: | No. 14 | ||||
Page Range: | pp. 2421-2432 | ||||
DOI: | 10.1038/emboj.2010.120 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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