Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons

Koppers, Max; Cagnetta, Roberta; Shigeoka, Toshiaki; Wunderlich, Lucia Cs; Ramirez, Pedro P. Vallejo; Lin, Julie Qiaojin; Zhao, Sixian; Jakobs, Maximilian Ah; Dwivedy, Asha; Minett, Michael S.; Bellon, Anaïs; Kaminski, Clemens F.; Harris, William A.; Flanagan, John G.; Holt, Christine E.

doi:10.7554/elife.48718

Cited by 48 publications

(45 citation statements)

References 59 publications

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“…Consistent with the imaging data above, RAB13 RNA is significantly enriched at extending protrusions while, still, RAB13 protein is not (Fig 1D). We additionally considered whether acute stimulation might lead to a transient increase in peripheral RAB13 protein, since RNA translation can be locally induced upon activation of specific cell surface receptors (Huttelmaier et al , 2005; Cagnetta et al , 2018; Koppers et al , 2019). Again, however, we do not observe any increase in the amount of RAB13 protein at protrusions or in the overall RAB13 protein levels, upon stimulation with serum (Fig EV1).…”

Section: Resultsmentioning

confidence: 99%

RNA localization and co‐translational interactions control RAB 13 GTP ase function and cell migration

et al. 2020

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Numerous RNA s exhibit specific distribution patterns in mammalian cells. However, the functional and mechanistic consequences are relatively unknown. Here, we investigate the functional role of RNA localization at cellular protrusions of migrating mesenchymal cells, using as a model the RAB 13 RNA , which encodes a GTP ase important for vesicle‐mediated membrane trafficking. While RAB 13 RNA is enriched at peripheral protrusions, the expressed protein is concentrated perinuclearly. By specifically preventing RAB 13 RNA localization, we show that peripheral RAB 13 translation is not important for the overall distribution of the RAB 13 protein or its ability to associate with membranes, but is required for full activation of the GTP ase and for efficient cell migration. RAB 13 translation leads to a co‐translational association of nascent RAB 13 with the exchange factor RABIF . Our results indicate that RAB 13‐ RABIF association at the periphery is required for directing RAB 13 GTP ase activity to promote cell migration. Thus, translation of RAB 13 in specific subcellular environments imparts the protein with distinct properties and highlights a means of controlling protein function through local RNA translation.

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Section: Resultsmentioning

confidence: 99%

RNA localization and co‐translational interactions control RAB 13 GTP ase function and cell migration

et al. 2020

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“…The remaining ∼25% that undergo the same translational change regardless of the valence of the cue point to conserved aspects of attractive and repulsive axon guidance. In a later study, proteomic analysis of the guidance cue receptor interactomes revealed that different receptors interact with specific ribosomes, mRNAs, and mRNA binding proteins, which may explain the unique translational signature of each guidance cue (Koppers et al, 2019). These studies add to a rich and growing body of literature tackling the role of de novo peptide synthesis and axonal protein transport in axon guidance across model organisms (Poulopoulos et al, 2019;Schiapparelli et al, 2019).…”

Section: Axon Guidancementioning

confidence: 89%

Advances in Proteomics Allow Insights Into Neuronal Proteomes

Fingleton

Roche

2021

Front. Mol. Neurosci.

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Protein–protein interaction networks and signaling complexes are essential for normal brain function and are often dysregulated in neurological disorders. Nevertheless, unraveling neuron- and synapse-specific proteins interaction networks has remained a technical challenge. New techniques, however, have allowed for high-resolution and high-throughput analyses, enabling quantification and characterization of various neuronal protein populations. Over the last decade, mass spectrometry (MS) has surfaced as the primary method for analyzing multiple protein samples in tandem, allowing for the precise quantification of proteomic data. Moreover, the development of sophisticated protein-labeling techniques has given MS a high temporal and spatial resolution, facilitating the analysis of various neuronal substructures, cell types, and subcellular compartments. Recent studies have leveraged these novel techniques to reveal the proteomic underpinnings of well-characterized neuronal processes, such as axon guidance, long-term potentiation, and homeostatic plasticity. Translational MS studies have facilitated a better understanding of complex neurological disorders, such as Alzheimer’s disease (AD), Schizophrenia (SCZ), and Autism Spectrum Disorder (ASD). Proteomic investigation of these diseases has not only given researchers new insight into disease mechanisms but has also been used to validate disease models and identify new targets for research.

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“…HnRNPs are also involved in regulating specific axonal translation. For instance, hnRNP A2/B1 was found to interact with Netrin-1 DCC, which binds a subset of mRNAs involved in cell-cell adhesion and protein targeting, inducing the translation of specific subsets of mRNAs [69,70]. HnRNP H1, H2, and F are also involved in regulating axonal mRNA regulation [71].…”

Section: Axonal Transportmentioning

confidence: 99%

Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases

et al. 2020

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Heterogenous nuclear ribonucleoproteins (hnRNPs) are a complex and functionally diverse family of RNA binding proteins with multifarious roles. They are involved, directly or indirectly, in alternative splicing, transcriptional and translational regulation, stress granule formation, cell cycle regulation, and axonal transport. It is unsurprising, given their heavy involvement in maintaining functional integrity of the cell, that their dysfunction has neurological implications. However, compared to their more established roles in cancer, the evidence of hnRNP implication in neurological diseases is still in its infancy. This review aims to consolidate the evidences for hnRNP involvement in neurological diseases, with a focus on spinal muscular atrophy (SMA), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), multiple sclerosis (MS), congenital myasthenic syndrome (CMS), and fragile X-associated tremor/ataxia syndrome (FXTAS). Understanding more about hnRNP involvement in neurological diseases can further elucidate the pathomechanisms involved in these diseases and perhaps guide future therapeutic advances.

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Receptor-specific interactome as a hub for rapid cue-induced selective translation in axons

Cited by 48 publications

References 59 publications

RNA localization and co‐translational interactions control RAB 13 GTP ase function and cell migration

RNA localization and co‐translational interactions control RAB 13 GTP ase function and cell migration

Advances in Proteomics Allow Insights Into Neuronal Proteomes

Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases

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