Dynamic Expression of Genes Encoding Ubiquitin Conjugating Enzymes (E2s) During Neuronal Differentiation and Maturation: Implications for Neurodevelopmental Disorders and Neurodegenerative Diseases

被引:1
作者
Paubel, Agathe [1 ]
Marouillat, Sylviane [1 ]
Dangoumau, Audrey [1 ]
Maurel, Cindy [1 ]
Haouari, Shanez [1 ]
Blasco, Helene [1 ,2 ]
Corcia, Philippe [1 ,3 ]
Laumonnier, Frederic [1 ]
Andres, Christian R. [1 ,2 ]
Vourc'h, Patrick [1 ,2 ]
机构
[1] Univ Tours, INSERM, Imaging Brain & Neuropsychiat IBraiN U1253, F-37044 Tours, France
[2] CHU Tours, Serv Biochim & Biol Mol, F-37032 Tours, France
[3] CHU Tours, Ctr SLA, Serv Neurol, F-37032 Tours, France
关键词
post-translational modifications; ubiquitin; SUMO; intellectual disability; Alzheimer; Parkinson; amyotrophic lateral sclerosis; PROTEIN; MUTATIONS; DEGRADATION; PROTEASOME; IDENTIFICATION; SUMOYLATION; PLASTICITY; POLARITY; UBE2A;
D O I
10.3390/genes15111381
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: The ubiquitination process plays a crucial role in neuronal differentiation and function. Numerous studies have focused on the expression and functions of E3 ligases during these different stages, far fewer on E2 conjugating enzymes. In mice, as in humans, these E2s belong to 17 conjugating enzyme families. Objectives: We analyzed by real-time PCR the expression dynamics of all known E2 genes during an in vitro differentiation of mouse hippocampal neuronal cultures, and after, we analyzed their stimulation with N-methyl-D-aspartate (NMDA). Results: We found that 36 of the 38 E2 genes were expressed in hippocampal neurons. Many were up-regulated during neuritogenesis and/or synaptogenesis stages, such as Ube2h, Ube2b, and Aktip. Rapid and delayed responses to NMDA stimulation were associated with the increased expression of several E2 genes, such as Ube2i, the SUMO-conjugating E2 enzyme. We also observed similar expression profiles within the same E2 gene family, consistent with the presence of similar transcription factor binding sites in their respective promoter sequences. Conclusions: Our study indicates that specific expression profiles of E2 genes are correlated with changes in neuronal differentiation and activity. A better understanding of the regulation and function of E2s is needed to better understand the role played by the ubiquitination process in physiological mechanisms and pathophysiological alterations involved in neurodevelopmental or neurodegenerative diseases.
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页数:15
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