NDE1 and NDEL1 from genes to (mal)functions: parallel but distinct roles impacting on neurodevelopmental disorders and psychiatric illness

NDE1 and NDEL1 from genes to (mal)functions: parallel but distinct roles impacting on neurodevelopmental disorders and psychiatric illness

Author Bradshaw, Nicholas J. Google Scholar
Hayashi, Mirian A. F. Autor UNIFESP Google Scholar
Abstract NDE1 (Nuclear Distribution Element 1, also known as NudE) and NDEL1 (NDE-Like 1, also known as NudEL) are the mammalian homologues of the fungus nudE gene, with important and at least partially overlapping roles for brain development. While a large number of studies describe the various properties and functions of these proteins, many do not directly compare the similarities and differences between NDE1 and NDEL1. Although sharing a high degree structural similarity and multiple common cellular roles, each protein presents several distinct features that justify their parallel but also unique functions. Notably both proteins have key binding partners in dynein, LIS1 and DISC1, which impact on neurodevelopmental and psychiatric illnesses. Both are implicated in schizophrenia through genetic and functional evidence, with NDE1 also strongly implicated in microcephaly, as well as other neurodevelopmental and psychiatric conditions through copy number variation, while NDEL1 possesses an oligopeptidase activity with a unique potential as a biomarker in schizophrenia. In this review, we aim to give a comprehensive overview of the various cellular roles of these proteins in a "bottom-up" manner, from their biochemistry and protein-protein interactions on the molecular level, up to the consequences for neuronal differentiation, and ultimately to their importance for correct cortical development, with direct consequences for the pathophysiology of neurodevelopmental and mental illness.
Keywords Dynein
Microtubules
Neurodevelopment
Neuron differentiation
Oligopeptidase activity
Schizophrenia
xmlui.dri2xhtml.METS-1.0.item-coverage Basel
Language English
Sponsor Forschungskommission der Medizinischen Fakultat der Heinrich-Heine-Universitat Dusseldorf
Fritz Thyssen Stiftung
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Grant number Forschungskommission der Medizinischen Fakultat der Heinrich-Heine-Universitat Dusseldorf: 9772547
Fritz Thyssen Stiftung: 10.14.2.140
CNPq: 477760/2010-4
CNPq: 557753/2010-4
CNPq: 508113/2010-5
CNPq: 311815/2012-0
CNPq: 475739/2013-2
Date 2017
Published in Cellular And Molecular Life Sciences. Basel, v. 74, n. 7, p. 1191-1210, 2017.
ISSN 1420-682X (Sherpa/Romeo, impact factor)
Publisher Springer Basel Ag
Extent 1191-1210
Origin http://dx.doi.org/10.1007/s00018-016-2395-7
Access rights Closed access
Type Article
Web of Science ID WOS:000397495700003
URI https://repositorio.unifesp.br/handle/11600/54857

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