Assessing the role of endooligopeptidase activity of Ndel1 (nuclear-distribution gene E homolog like-1) in neurite outgrowth

Assessing the role of endooligopeptidase activity of Ndel1 (nuclear-distribution gene E homolog like-1) in neurite outgrowth

Author Hayashi, Mirian A. F. Autor UNIFESP Google Scholar
Guerreiro, Juliano R. Google Scholar
Charych, Erik Google Scholar
Kamiya, Atsushi Google Scholar
Barbosa, Rosicler L. Google Scholar
Machado, Mauricio F. Autor UNIFESP Google Scholar
Campeiro, Joana D. Google Scholar
Oliveira, Vitor Autor UNIFESP Google Scholar
Sawa, Akira Google Scholar
Camargo, Antonio C. M. Google Scholar
Brandon, Nicholas J. Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Inst Butantan
Johns Hopkins Univ
Pfizer Global R&D
Abstract Ndel1 plays multiple roles in neuronal development but it is unknown whether its reported cysteine protease activity is important for these processes. Ndel1 is known to be critical for neurite outgrowth in PC12 cells where it works co-operatively in a complex with DISCI to allow normal neuritogenesis. Through an initial interest in understanding the regulation of the expression of Ndel1 during neuronal differentiation, we have been able to show that Ndel1 expression and enzyme activity is up-regulated during neurite outgrowth in PC12 cells induced to neural differentiation. Heterologous expression of wild-type Ndel1 (Ndel1(WT)) in PC12 cells increases the percentage of cells bearing neurites in contrast to the catalytically dead mutant, Ndel1(C273A), which caused a decrease. Furthermore depletion of endogenous Ndel1 by RNAi decreased neurite outgrowth, which was rescued by transfection of the enzymatically active Ndel1(WT), but not by the Ndel1(C273A) mutant. Together these data support the notion that the endooligopeptidase activity of Ndel1 plays a crucial role in the differentiation process of PC12 cells to neurons. Genetic data and protein interaction with DISCI might suggest a role for Ndel1 in neuropsychiatirc conditions. (C) 2010 Elsevier Inc. All rights reserved.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
S-R foundation
Grant number NIH: MH084018
NIH: MH069853
Date 2010-08-01
Published in Molecular and Cellular Neuroscience. San Diego: Academic Press Inc Elsevier Science, v. 44, n. 4, p. 353-361, 2010.
ISSN 1044-7431 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 353-361
Access rights Closed access
Type Article
Web of Science ID WOS:000279525600005

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