Decreased anxiety-related behaviour but apparently unperturbed NUMB function in ligand of NUMB protein-X (LNX) 1/2 double knockout mice

Show simple item record Lenihan, Joan A. Saha, Orthis Heimer-McGinn, Victoria Cryan, John F. Feng, Guoping Young, Paul W. 2017-01-24T09:21:00Z 2017-01-24T09:21:00Z 2016-11-26
dc.identifier.citation Lenihan, J. A., Saha, O., Heimer-McGinn, V., Cryan, J. F., Feng, G. and Young, P. W. (2016) 'Decreased anxiety-related behaviour but apparently unperturbed NUMB function in ligand of NUMB protein-X (LNX) 1/2 double knockout mice', Molecular Neurobiology, 54(10), pp. 8090-8109. doi:10.1007/s12035-016-0261-0 en
dc.identifier.volume 54
dc.identifier.issued 10
dc.identifier.startpage 8090
dc.identifier.endpage 8109
dc.identifier.issn 0893-7648
dc.identifier.doi 10.1007/s12035-016-0261-0
dc.description.abstract NUMB is a key regulator of neurogenesis and neuronal differentiation that can be ubiquitinated and targeted for proteasomal degradation by ligand of numb protein-X (LNX) family E3 ubiquitin ligases. However, our understanding of LNX protein function in vivo is very limited. To examine the role of LNX proteins in regulating NUMB function in vivo, we generated mice lacking both LNX1 and LNX2 expression in the brain. Surprisingly, these mice are healthy, exhibit unaltered levels of NUMB protein and do not display any neuroanatomical defects indicative of aberrant NUMB function. Behavioural analysis of LNX1/LNX2 double knockout mice revealed decreased anxiety-related behaviour, as assessed in the open field and elevated plus maze paradigms. By contrast, no major defects in learning, motor or sensory function were observed. Given the apparent absence of major NUMB dysfunction in LNX null animals, we performed a proteomic analysis to identify neuronal LNX-interacting proteins other than NUMB that might contribute to the anxiolytic phenotype observed. We identified and/or confirmed interactions of LNX1 and LNX2 with proteins known to have presynaptic and neuronal signalling functions, including the presynaptic active zone constituents ERC1, ERC2 and LIPRIN-αs (PPFIA1, PPFIA3), as well as the F-BAR domain proteins FCHSD2 (nervous wreck homologue) and SRGAP2. These and other novel LNX-interacting proteins identified are promising candidates to mediate LNX functions in the central nervous system, including their role in modulating anxiety-related behaviour. en
dc.description.sponsorship Science Foundation Ireland (Research Frontiers Programme grant 08/RFP/ NSC1382); Irish Research Council (EMBARK Postgraduate Research Scholarship) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Springer Science+Business Media en
dc.rights © 2016, Springer Science+Business Media New York. The final publication is available at Springer via 10.1007/s12035-016-0261-0 en
dc.subject LNX1 en
dc.subject LNX2 en
dc.subject LIPRIN/PPFIA en
dc.subject ERC1/ERC2 en
dc.subject NUMB en
dc.subject Anxiety en
dc.title Decreased anxiety-related behaviour but apparently unperturbed NUMB function in ligand of NUMB protein-X (LNX) 1/2 double knockout mice en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Paul Young, Biochemistry & Cell Biology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: en
dc.internal.availability Full text available en Access to this article is restricted until 12 months after publication by request of the publisher. en 2017-11-26 2017-01-23T13:47:42Z
dc.description.version Accepted Version en
dc.internal.rssid 380746160
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Irish Research Council en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Molecular Neurobiology en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress en

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