The E3‐ubiquitin ligase TRIM2 regulates neuronal polarization

Khazaei, Mohamad; Bunk, Eva C.; Hillje, Anna-Lena; Jahn, Henriette; Riegler, Eva M.; Knoblich, Juergen A.; Young, Peter; Schwamborn, Jens Christian

doi:10.1111/j.1471-4159.2010.06971.x

Cited by 44 publications

(39 citation statements)

References 25 publications

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“…TRIM2 is a member of the TRIM superfamily mainly expressed in the brain [18,44] containing a RING finger, B-box, and coiled-coil domains in the amino terminus. TRIM2 interacts with NF-L and regulates its metabolism by ubiquitination [8]. Here, we found that the TRIM2 expression was positively correlated with the NF-L ubiquitination level and negatively correlated with the NF-L expression, which was in line with previous studies [19].…”

Section: Discussionsupporting

confidence: 92%

“…According to the prediction of microRNA target gene, tripartite motif 2 (TRIM2) is one of the potential downstream targets of miR-181c [6]. TRIM2 is one of the E3 ubiquitin ligases highly expressed in the hippocampus [7], and neurofilament light (NF-L) is one of the ubiquitination targets of TRIM2 [8]. As the neuronal intermediate filament protein expressed both in the dendrite and the axon, NF-L is closely related to the dendritic branching and dendrite spine formation [9].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

Chen

Min

et al. 2016

Mol Neurobiol

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Chronic cerebral hypoperfusion (CCH) characterized by global cerebral ischemia is an important risk factor contributing to the development of dementia. MicroRNAs (miRNAs) play important roles in the cellular adaptation to long-term ischemia/hypoxia by turning off or on the expression of target genes. MiR-181c is widely expressed in the nervous system, and tripartite motif 2 (TRIM2) is one of its target genes. In this work, we had identified that progressive spatial memory deficiency was induced in the bilateral common carotid artery occlusion (2-VO) rat models. Meanwhile, inhibition of miR-181c expression and upregulation of TRIM2 in the hippocampus of 2-VO rats were found accompanying with reduction in the dendritic branching and dendrite spine density of the hippocampal neurons. Viral vector-mediated miR-181c delivery might improve the cognitive deficiency via TRIM2 on neurofilament light (NF-L) ubiquitination resulting in remodeling of the hippocampal neurons as well as increase in N-methyl-D-aspartate receptor 1 (NR1) subunit cell surface expression. Meanwhile, miR-181c might rescue the cellular activity from ischemia/hypoxia. These results indicated a novel miRNA-mediated mechanism involving miR-181c and TRIM2 in the cognitive impairment induced by CCH and provided a rationale for the development of miRNA-based strategies for prevention of dementia.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

Chen

Min

et al. 2016

Mol Neurobiol

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“…TRIM2 has been shown to participate in neuronal plasticity, 37 axon initialization 38 and ubiquitination of the neurofilament light subunit. 39 TRIM2 -deficient mice have greater levels of neurofilament light subunit in axons and resulting axonal swellings in the cerebellum, retina, spinal cord and cerebral cortex, leading to progressive neurodegeneration with juvenile-onset tremor and ataxia.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of severity in multiple sclerosis

Briggs¹,

Shao²,

Goldstein³

et al. 2011

Genes Immun

106

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Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system with a strong genetic component. Several lines of evidence support a strong role for genetic factors influencing both disease susceptibility and clinical outcome in MS. Identification of genetic variants that distinguish particular disease subgroups and/or predict a severe clinical outcome is critical to further our understanding of disease mechanisms and guide development of effective therapeutic approaches. We studied 1470 MS cases and performed a genome-wide association study of more than 2.5 million single-nucleotide polymorphisms to identify loci influencing disease severity, measured using the MS severity score (MSSS), a measure of clinical disability. Of note, no single result achieved genome-wide significance. Furthermore, variants within previously confirmed MS susceptibility loci do not appear to influence severity. Although bioinformatic analyses highlight certain pathways that are over-represented in our results, we conclude that the genetic architecture of disease severity is likely polygenic and comprised of modest effects, similar to what has been described for MS susceptibility, to date. However, a role for major effects of rare variants cannot be excluded. Importantly, our results also show the MSSS, when considered as a binary or continuous phenotype variable is by comparison a stable outcome.

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“…It is now evident from multiple studies that cellular proteolytic machinery is exquisitely implicated in the formation of synapses and neuronal circuitry, by maintaining the polarity of neurons (Murphey and Godenschwege, 2002; Bingol and Schuman, 2005). Several crucial E3 ubiquitin ligases, viz., TRIM2, TRIM46, and FBXO31-SCF, have been found to have a regulatory control over migration, polarization and synapse formation (Khazaei et al, 2011; Vadhvani et al, 2013; van Beuningen et al, 2015). A number of reports postulate the decisive involvement of PQC system in the maintenance of cellular proteostasis, and thus in ameliorating the toxicities generated by the accumulation of misfolded proteins in late-age.…”

Section: Key Questions and Future Prospectivementioning

confidence: 99%

E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

Upadhyay

Joshi

Amanullah

et al. 2017

Front. Mol. Neurosci.

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Cells regularly synthesize new proteins to replace old or damaged proteins. Deposition of various aberrant proteins in specific brain regions leads to neurodegeneration and aging. The cellular protein quality control system develop various defense mechanisms against the accumulation of misfolded and aggregated proteins. The mechanisms underlying the selective recognition of specific crucial protein or misfolded proteins are majorly governed by quality control E3 ubiquitin ligases mediated through ubiquitin-proteasome system. Few known E3 ubiquitin ligases have shown prominent neurodevelopmental functions, but their interactions with different developmental proteins play critical roles in neurodevelopmental disorders. Several questions are yet to be understood properly. How E3 ubiquitin ligases determine the specificity and regulate degradation of a particular substrate involved in neuronal proliferation and differentiation is certainly the one, which needs detailed investigations. Another important question is how neurodevelopmental E3 ubiquitin ligases specifically differentiate between their versatile range of substrates and timing of their functional modulations during different phases of development. The premise of this article is to understand how few E3 ubiquitin ligases sense major molecular events, which are crucial for human brain development from its early embryonic stages to throughout adolescence period. A better understanding of these few E3 ubiquitin ligases and their interactions with other potential proteins will provide invaluable insight into disease mechanisms to approach toward therapeutic interventions.

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The E3‐ubiquitin ligase TRIM2 regulates neuronal polarization

Cited by 44 publications

References 25 publications

MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

MicroRNA-181c Ameliorates Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

Genome-wide association study of severity in multiple sclerosis

E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

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