Activity-regulated E3 ubiquitin ligase TRIM47 modulates excitatory synapse development

Sharma, Gourav Prateek; Banerjee, Sourav

doi:10.3389/fnmol.2022.943980

Cited by 4 publications

(3 citation statements)

References 69 publications

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“…In healthy brains, TRIM47 is developmentally regulated to facilitate hippocampal synapse development ( Sharma and Banerjee, 2022 ). In adults, however, TRIM47 is more strongly localized to brain blood vessel endothelial cells, which may impact tumor growth by delivering oxygen and nutrients to the expanding tumor mass, thus correlating with increased TRIM47 expression in higher grade gliomas, although this has not yet been explored ( Hanahan and Weinberg, 2011 ; Hao et al, 2019 ; Ji et al, 2021 ; Mishra et al, 2022 ).…”

Section: The Impact Of Trims On Aberrant Cell Division and Cancer In ...mentioning

confidence: 99%

It’s a TRIM-endous view from the top: the varied roles of TRIpartite Motif proteins in brain development and disease

Dudley-Fraser,

Rittinger

2023

Front. Mol. Neurosci.

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The tripartite motif (TRIM) protein family members have been implicated in a multitude of physiologies and pathologies in different tissues. With diverse functions in cellular processes including regulation of signaling pathways, protein degradation, and transcriptional control, the impact of TRIM dysregulation can be multifaceted and complex. Here, we focus on the cellular and molecular roles of TRIMs identified in the brain in the context of a selection of pathologies including cancer and neurodegeneration. By examining each disease in parallel with described roles in brain development, we aim to highlight fundamental common mechanisms employed by TRIM proteins and identify opportunities for therapeutic intervention.

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Section: The Impact Of Trims On Aberrant Cell Division and Cancer In ...mentioning

confidence: 99%

It’s a TRIM-endous view from the top: the varied roles of TRIpartite Motif proteins in brain development and disease

Dudley-Fraser,

Rittinger

2023

Front. Mol. Neurosci.

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“…, 2023 ). Of note, several recent studies specifically identify members of the Tripartate Motif (TRIM) family of E3 ubiquitin ligases at the synapse ( Sharma and Banerjee, 2022 ; Gay et al. , 2023 ; McCormick et al.…”

Section: Introductionmentioning

confidence: 99%

The E3 ubiquitin ligase TRIM9 regulates synaptic function and actin dynamics in response to netrin-1

McCormick,

Evans,

Barker

et al. 2024

MBoC

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During neuronal development, dynamic filopodia emerge from dendrites and mature into functional dendritic spines during synaptogenesis. Dendritic filopodia and spines respond to extracellular cues, influencing dendritic spine shape and size as well as synaptic function. Previously, the E3 ubiquitin ligase TRIM9 was shown to regulate filopodia in early stages of neuronal development, including netrin-1 dependent axon guidance and branching. Here we demonstrate TRIM9 also localizes to dendritic filopodia and spines of murine cortical and hippocampal neurons during synaptogenesis and is required for synaptic responses to netrin. In particular, TRIM9 is enriched in the post-synaptic density (PSD) within dendritic spines and loss of Trim9 alters the PSD proteome, including the actin cytoskeleton landscape. While netrin exposure induces accumulation of the Arp2/3 complex and filamentous actin in dendritic spine heads, this response is disrupted by genetic deletion of Trim9. In addition, we document changes in the synaptic receptors associated with loss of Trim9. These defects converge on a loss of netrin-dependent increases in neuronal firing rates, indicating TRIM9 is required downstream of synaptic netrin-1 signaling. We propose TRIM9 regulates cytoskeletal dynamics in dendritic spines and is required for the proper response to synaptic stimuli.

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“…Within neurons, E3 ligases influence the neuronal proteome and they are known to control various aspects of neuronal development; including neurogenesis [20][21][22], neurite development [23][24][25]; regulation of neuronal morphogenesis [26][27][28], synapse formation [29][30][31][32]; synapse pruning [33,34] and in both Hebbian [35] and homeostatic [36,37] [31] forms of synaptic plasticity; among others. Aberrations in E3 ligase functions have been linked to disorders involved in neuronal development [38][39][40] as well as neurodegeneration [41][42][43][44].…”

Section: Introductionmentioning

confidence: 99%

The RNA binding ubiquitination ligase MEX3B regulates bFGF-dependent neuronal proliferation

Garg,

Sharma,

Samaddar

et al. 2024

Preprint

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BackgroundE3 ubiquitin ligases, integral components of the proteasomal degradation cascade, are critical for regulating the cellular proteome via canonical proteasome-mediated protein degradation; however, the non-canonical functions of these ligases in neuronal development are poorly understood. Our study focuses on a special class of E3 ubiquitin ligases known as RNA Binding Ubiquitin Ligases (RBUL) that harbour RNA-binding domains; allowing them to acquire all the properties of RNA-binding proteins (RBPs) and regulate transcriptional or post-transcriptional changes associated with the control of gene expression in cellular phenotypes. We aim to identify one such RUBL in the context of the highly dynamic yet stringently controlled process of neural proliferation and neural fate determination.ResultsMEX3B protein is a member of the MEX3 family and a part of the RBUL class of E3 ligases. It is differentially expressed in Neural Progenitor Cells (NPCs) upon differentiation. Mex3b RNA and protein were found to have temporally opposing expression patterns in presence of basic fibroblast growth factor (bFGF), a key signalling protein involved in neuronal proliferation. MEX3B is required for maintenance of the proliferative state of NPCs, whereas, its knockdown promotes transition from proliferative to differentiation state even in presence of bFGF that restricts differentiation. Furthermore, the knockdown of MEX3B protein results in the appearance of morphological hallmarks associated with early stages of neuronal differentiation including increase in neurite length and complexity. MEX3B interacts with the pro-proliferative transcription activator REST and the long non-coding RNA,HOTAIR. The study suggests the existence of a bFGF-dependent, combinatorial axis involving Mex3b, REST andHOTAIR, for the maintenance of NPC proliferative states.ConclusionMEX3B, containing RNA binding motifs, is a unique E3 ligase that is necessary for bFGF-dependent proliferation. Mex3b protein invokes its non-canonical function of an RNA binding protein to form a tripartite complex with the transcription activator REST andHOTAIRlncRNA to define the proliferative state of NPCs. The study highlights a unique feature of special E3 ligases in neuronal proliferation during brain development that was previously overlooked.

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Activity-regulated E3 ubiquitin ligase TRIM47 modulates excitatory synapse development

Cited by 4 publications

References 69 publications

It’s a TRIM-endous view from the top: the varied roles of TRIpartite Motif proteins in brain development and disease

It’s a TRIM-endous view from the top: the varied roles of TRIpartite Motif proteins in brain development and disease

The E3 ubiquitin ligase TRIM9 regulates synaptic function and actin dynamics in response to netrin-1

The RNA binding ubiquitination ligase MEX3B regulates bFGF-dependent neuronal proliferation

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