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Article ; Online: Local BMP signaling: A sensor for synaptic activity that balances synapse growth and function.

Vicidomini, Rosario / Serpe, Mihaela

2022 Volume 150, Page(s) 211–254

Abstract: Synapse development is coordinated by intercellular communication between the pre- and postsynaptic compartments, and by neuronal activity itself. In flies as in vertebrates, neuronal activity induces input-specific changes in the synaptic strength so ... ...

Abstract	Synapse development is coordinated by intercellular communication between the pre- and postsynaptic compartments, and by neuronal activity itself. In flies as in vertebrates, neuronal activity induces input-specific changes in the synaptic strength so that the entire circuit maintains stable function in the face of many challenges, including changes in synapse number and strength. But how do neurons sense synapse activity? In several studies carried out using the Drosophila neuromuscular junction (NMJ), we demonstrated that local BMP signaling provides an exquisite sensor for synapse activity. Here we review the main features of this exquisite sensor and discuss its functioning beyond monitoring the synapse activity but rather as a key controller that operates in coordination with other BMP signaling pathways to balance synapse growth, maturation and function.
MeSH term(s)	Animals ; Drosophila/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster ; Neuromuscular Junction ; Signal Transduction/physiology ; Synapses
Chemical Substances	Drosophila Proteins
Language	English
Publishing date	2022-05-18
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Intramural
ISSN	1557-8933 ; 0070-2153
ISSN (online)	1557-8933
ISSN	0070-2153
DOI	10.1016/bs.ctdb.2022.04.001
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Article ; Online: New Insights into Dyskerin-CypA Interaction: Implications for X-Linked Dyskeratosis Congenita and Beyond.

Belli, Valentina / Maiello, Daniela / Di Lorenzo, Concetta / Furia, Maria / Vicidomini, Rosario / Turano, Mimmo

Genes

2023 Volume 14, Issue 9

Abstract: The highly conserved family of cyclophilins comprises multifunctional chaperones that interact with proteins and RNAs, facilitating the dynamic assembly of multimolecular complexes involved in various cellular processes. Cyclophilin A (CypA), the ... ...

Abstract	The highly conserved family of cyclophilins comprises multifunctional chaperones that interact with proteins and RNAs, facilitating the dynamic assembly of multimolecular complexes involved in various cellular processes. Cyclophilin A (CypA), the predominant member of this family, exhibits peptidyl-prolyl cis-trans isomerase activity. This enzymatic function aids with the folding and activation of protein structures and often serves as a molecular regulatory switch for large multimolecular complexes, ensuring appropriate inter- and intra-molecular interactions. Here, we investigated the involvement of CypA in the nucleus, where it plays a crucial role in supporting the assembly and trafficking of heterogeneous ribonucleoproteins (RNPs). We reveal that CypA is enriched in the nucleolus, where it colocalizes with the pseudouridine synthase dyskerin, the catalytic component of the multifunctional H/ACA RNPs involved in the modification of cellular RNAs and telomere stability. We show that dyskerin, whose mutations cause the X-linked dyskeratosis (X-DC) and the Hoyeraal-Hreidarsson congenital ribosomopathies, can directly interact with CypA. These findings, together with the remark that substitution of four dyskerin prolines are known to cause X-DC pathogenic mutations, lead us to indicate this protein as a CypA client. The data presented here suggest that this chaperone can modulate dyskerin activity influencing all its partecipated RNPs.
MeSH term(s)	Humans ; Catalysis ; Cyclophilin A ; Dyskeratosis Congenita/genetics ; Ribonucleoproteins ; RNA-Binding Proteins
Chemical Substances	Cyclophilin A (EC 5.2.1.-) ; Ribonucleoproteins ; RNA-Binding Proteins ; DKC1 protein, human
Language	English
Publishing date	2023-09-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14091766
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Article ; Online: scRNA-seq data from the larval Drosophila ventral cord provides a resource for studying motor systems function and development.

Nguyen, Tho Huu / Vicidomini, Rosario / Choudhury, Saumitra Dey / Han, Tae Hee / Maric, Dragan / Brody, Thomas / Serpe, Mihaela

Developmental cell

2024 Volume 59, Issue 9, Page(s) 1210–1230.e9

Abstract: The Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. Here, we use high-quality scRNA-seq, validated ... ...

Abstract	The Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. Here, we use high-quality scRNA-seq, validated by anatomical identification, to create a comprehensive census of larval VNC cell types. We show that the neural lineages that comprise the adult VNC are already defined, but quiescent, at the larval stage. Using fluorescence-activated cell sorting (FACS)-enriched populations, we separate all motor neuron bundles and link individual neuron clusters to morphologically characterized known subtypes. We discovered a glutamate receptor subunit required for basal neurotransmission and homeostasis at the larval neuromuscular junction. We describe larval glia and endorse the general view that glia perform consistent activities throughout development. This census represents an extensive resource and a powerful platform for future discoveries of cellular and molecular mechanisms in repair, regeneration, plasticity, homeostasis, and behavioral coordination.
MeSH term(s)	Animals ; Larva/genetics ; Larva/metabolism ; Motor Neurons/metabolism ; Motor Neurons/cytology ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Neuroglia/metabolism ; Neuroglia/cytology ; Neuromuscular Junction/metabolism ; Drosophila Proteins/metabolism ; Drosophila Proteins/genetics ; RNA-Seq/methods ; Single-Cell Gene Expression Analysis
Chemical Substances	Drosophila Proteins
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2024.03.016
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Zs.A 5742: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: The Epithelial to Mesenchymal Transition in Colorectal Cancer Progression: The Emerging Role of Succinate Dehydrogenase Alterations and Succinate Accumulation.

Turano, Mimmo / Vicidomini, Rosario / Cammarota, Francesca / D'Agostino, Valeria / Duraturo, Francesca / Izzo, Paola / Rosa, Marina De

Biomedicines

2023 Volume 11, Issue 5

Abstract: Colorectal cancer (CRC) stands as the third most significant contributor to cancer-related mortality worldwide. A major underlying reason is that the detection of CRC usually occurs at an advanced metastatic stage, rendering therapies ineffective. In the ...

Abstract	Colorectal cancer (CRC) stands as the third most significant contributor to cancer-related mortality worldwide. A major underlying reason is that the detection of CRC usually occurs at an advanced metastatic stage, rendering therapies ineffective. In the progression from the in situ neoplasia stage to the advanced metastatic stage, a critical molecular mechanism involved is the epithelial-to-mesenchymal transition (EMT). This intricate transformation consists of a series of molecular changes, ultimately leading the epithelial cell to relinquish its features and acquire mesenchymal and stem-like cell characteristics. The EMT regulation involves several factors, such as transcription factors, cytokines, micro RNAs and long noncoding RNAs. Nevertheless, recent studies have illuminated an emerging link between metabolic alterations and EMT in various types of cancers, including colorectal cancers. In this review, we delved into the pivotal role played by EMT during CRC progression, with a focus on highlighting the relationship between the alterations of the tricarboxylic acid cycle, specifically those involving the succinate dehydrogenase enzyme, and the activation of the EMT program. In fact, emerging evidence supports the idea that elucidating the metabolic modifications that can either induce or inhibit tumor progression could be of immense significance for shaping new therapeutic approaches and preventative measures. We conclude that an extensive effort must be directed towards research for the standardization of drugs that specifically target proteins such as SDH and SUCNR1, but also TRAP1, PDH, ERK1/2, STAT3 and the HIF1-α catabolism.
Language	English
Publishing date	2023-05-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11051428
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Article ; Online: CAR T therapies in multiple myeloma: unleashing the future.

Sheykhhasan, Mohsen / Ahmadieh-Yazdi, Amirhossein / Vicidomini, Rosario / Poondla, Naresh / Tanzadehpanah, Hamid / Dirbaziyan, Ashkan / Mahaki, Hanie / Manoochehri, Hamed / Kalhor, Naser / Dama, Paola

Cancer gene therapy

2024 Volume 31, Issue 5, Page(s) 667–686

Abstract: In recent years, the field of cancer treatment has witnessed remarkable breakthroughs that have revolutionized the landscape of care for cancer patients. While traditional pillars such as surgery, chemotherapy, and radiation therapy have long been ... ...

Abstract	In recent years, the field of cancer treatment has witnessed remarkable breakthroughs that have revolutionized the landscape of care for cancer patients. While traditional pillars such as surgery, chemotherapy, and radiation therapy have long been available, a cutting-edge therapeutic approach called CAR T-cell therapy has emerged as a game-changer in treating multiple myeloma (MM). This novel treatment method complements options like autologous stem cell transplants and immunomodulatory medications, such as proteasome inhibitors, by utilizing protein complexes or anti-CD38 antibodies with potent complement-dependent cytotoxic effects. Despite the challenges and obstacles associated with these treatments, the recent approval of the second FDA multiple myeloma CAR T-cell therapy has sparked immense promise in the field. Thus far, the results indicate its potential as a highly effective therapeutic solution. Moreover, ongoing preclinical and clinical trials are exploring the capabilities of CAR T-cells in targeting specific antigens on myeloma cells, offering hope for patients with relapsed/refractory MM (RRMM). These advancements have shown the potential for CAR T cell-based medicines or combination therapies to elicit greater treatment responses and minimize side effects. In this context, it is crucial to delve into the history and functions of CAR T-cells while acknowledging their limitations. We can strategize and develop innovative approaches to overcome these barriers by understanding their challenges. This article aims to provide insights into the application of CAR T-cells in treating MM, shedding light on their potential, limitations, and strategies employed to enhance their efficacy.
MeSH term(s)	Multiple Myeloma/therapy ; Multiple Myeloma/immunology ; Humans ; Immunotherapy, Adoptive/methods ; Receptors, Chimeric Antigen/immunology
Language	English
Publishing date	2024-03-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1212513-1
ISSN	1476-5500 ; 0929-1903
ISSN (online)	1476-5500
ISSN	0929-1903
DOI	10.1038/s41417-024-00750-2
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Zs.A 4125: Show issues

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Article ; Online: Assembly and Exploration of a Single Cell Atlas of the Drosophila Larval Ventral Cord. Identification of Rare Cell Types.

Vicidomini, Rosario / Nguyen, Tho Huu / Choudhury, Saumitra Dey / Brody, Thomas / Serpe, Mihaela

Current protocols

2021 Volume 1, Issue 2, Page(s) e37

Abstract: Single-cell RNA sequencing provides a new approach to an old problem: how to study cellular diversity in complex biological systems. This powerful tool has been instrumental in profiling different cell types and investigating, at the single-cell level, ... ...

Abstract	Single-cell RNA sequencing provides a new approach to an old problem: how to study cellular diversity in complex biological systems. This powerful tool has been instrumental in profiling different cell types and investigating, at the single-cell level, cell states, functions, and responses. However, mining these data requires new analytical and statistical methods for high-dimensional analyses that must be customized and adapted to specific goals. Here we present a custom multistage analysis pipeline which integrates modules contained in different R packages to ensure flexible, high-quality RNA-seq data analysis. We describe this workflow step by step, providing the codes, explaining the rationale for each function, and discussing the results and the limitations. We apply this pipeline to analyze different datasets of Drosophila larval ventral cords, identifying and describing rare cell types, such as astrocytes and neuroendocrine cells. This multistage analysis pipeline can be easily implemented by both novice and experienced scientists interested in neuronal and/or cellular diversity beyond the Drosophila model system. © 2021 US Government.
MeSH term(s)	Animals ; Drosophila/genetics ; Gene Expression Profiling ; Larva/genetics ; Single-Cell Analysis ; Software
Language	English
Publishing date	2021-01-19
Publishing country	United States
Document type	Journal Article
ISSN	2691-1299
ISSN (online)	2691-1299
DOI	10.1002/cpz1.37
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Article: Dyskerin Downregulation Can Induce ER Stress and Promote Autophagy via AKT-mTOR Signaling Deregulation.

Maiello, Daniela / Varone, Marianna / Vicidomini, Rosario / Belli, Valentina / De Rosa, Marina / Dama, Paola / Furia, Maria / Turano, Mimmo

Biomedicines

2022 Volume 10, Issue 5

Abstract: Dyskerin is an evolutionarily conserved nucleolar protein implicated in a wide range of fundamental biological roles, including telomere maintenance and ribosome biogenesis. Germline mutations ... ...

Abstract	Dyskerin is an evolutionarily conserved nucleolar protein implicated in a wide range of fundamental biological roles, including telomere maintenance and ribosome biogenesis. Germline mutations of
Language	English
Publishing date	2022-05-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10051092
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Article ; Online: Single-Cell RNA Sequencing Analysis of the Drosophila Larval Ventral Cord.

Nguyen, Tho Huu / Vicidomini, Rosario / Choudhury, Saumitra Dey / Coon, Steven L / Iben, James / Brody, Thomas / Serpe, Mihaela

Current protocols

2021 Volume 1, Issue 2, Page(s) e38

Abstract: Drosophila provides a powerful genetic system and an excellent model to study the development and function of the nervous system. The fly's small brain and complex behavior has been instrumental in mapping neuronal circuits and elucidating the neural ... ...

Abstract	Drosophila provides a powerful genetic system and an excellent model to study the development and function of the nervous system. The fly's small brain and complex behavior has been instrumental in mapping neuronal circuits and elucidating the neural basis of behavior. The fast pace of fly development and the wealth of genetic tools has enabled systematic studies on cell differentiation and fate specification, and has uncovered strategies for axon guidance and targeting. The accessibility of neuronal structures and the ability to edit and manipulate gene expression in selective cells and/or synaptic compartments has revealed mechanisms for synapse assembly and neuronal connectivity. Recent advances in single-cell RNA sequencing (scRNA-seq) have further enhanced our appreciation and understanding of neuronal diversity in a fly brain. However, due to the small size of the fly brain and its constituent cells, scRNA-seq methodologies require a few adaptations. Here, we describe a set of protocols optimized for scRNA-seq analysis of the Drosophila larval ventral nerve cord, starting from tissue dissection and cell dissociation to cDNA library preparation, sequencing, and data analysis. We apply this workflow to three separate samples and detail the technical challenges associated with successful application of scRNA-seq to studies on neuronal diversity. An accompanying article (Vicidomini, Nguyen, Choudhury, Brody, & Serpe, 2021) presents a custom multistage analysis pipeline that integrates modules contained in different R packages to ensure high-flexibility, high-quality RNA-seq data analysis. These protocols are developed for Drosophila larval ventral nerve cord, but could easily be adapted to other tissues and model organisms. © 2021 U.S. Government. Basic Protocol 1: Dissection of larval ventral nerve cords and preparation of single-cell suspensions Basic Protocol 2: Preparation and sequencing of single-cell transcriptome libraries Basic Protocol 3: Alignment of raw sequencing data to indexed genome and generation of count matrices.
MeSH term(s)	Animals ; Drosophila/genetics ; Larva/genetics ; Sequence Analysis, RNA ; Single-Cell Analysis ; Software
Language	English
Publishing date	2021-02-25
Publishing country	United States
Document type	Journal Article
ISSN	2691-1299
ISSN (online)	2691-1299
DOI	10.1002/cpz1.38
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Article: A new role for human dyskerin in vesicular trafficking

Di Maio, Nunzia / Vicidomini, Rosario / Angrisani, Alberto / Belli, Valentina / Furia, Maria / Turano, Mimmo

FEBS Open Bio. 2017 Oct., v. 7, no. 10

2017

Abstract: Dyskerin is an essential, conserved, multifunctional protein found in the nucleolus, whose loss of function causes the rare genetic diseases X‐linked dyskeratosis congenita and Hoyeraal‐Hreidarsson syndrome. To further investigate the wide range of ... ...

Abstract	Dyskerin is an essential, conserved, multifunctional protein found in the nucleolus, whose loss of function causes the rare genetic diseases X‐linked dyskeratosis congenita and Hoyeraal‐Hreidarsson syndrome. To further investigate the wide range of dyskerin's biological roles, we set up stable cell lines able to trigger inducible protein knockdown and allow a detailed analysis of the cascade of events occurring within a short time frame. We report that dyskerin depletion quickly induces cytoskeleton remodeling and significant alterations in endocytic Ras‐related protein Rab‐5A/Rab11 trafficking. These effects arise in different cell lines well before the onset of telomere shortening, which is widely considered the main cause of dyskerin‐related diseases. Given that vesicular trafficking affects many homeostatic and differentiative processes, these findings add novel insights into the molecular mechanisms underlining the pleiotropic manifestation of the dyskerin loss‐of‐function phenotype.
Keywords	cell nucleolus ; cytoskeleton ; humans ; loss-of-function mutation ; phenotype ; telomeres
Language	English
Dates of publication	2017-10
Size	p. 1453-1468.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2651702-4
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.12307
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Human dyskerin: beyond telomeres.

Angrisani, Alberto / Vicidomini, Rosario / Turano, Mimmo / Furia, Maria

Biological chemistry

2014 Volume 395, Issue 6, Page(s) 593–610

Abstract: Human dyskerin is an evolutively conserved protein that participates in diverse nuclear complexes: the H/ACA snoRNPs, that control ribosome biogenesis, RNA pseudouridylation, and stability of H/ACA snoRNAs; the scaRNPs, that control pseudouridylation of ... ...

Abstract	Human dyskerin is an evolutively conserved protein that participates in diverse nuclear complexes: the H/ACA snoRNPs, that control ribosome biogenesis, RNA pseudouridylation, and stability of H/ACA snoRNAs; the scaRNPs, that control pseudouridylation of snRNAs; and the telomerase active holoenzyme, which safeguards telomere integrity. The biological importance of dyskerin is further outlined by the fact that its deficiency causes the X-linked dyskeratosis congenita disease, while its over-expression characterizes several types of cancers and has been proposed as prognostic marker. The role of dyskerin in telomere maintenance has widely been discussed, while its functions as H/ACA sno/scaRNP component has been so far mostly overlooked and represent the main goal of this review. Here we summarize how increasing evidence indicates that the snoRNA/microRNA pathways can be interlaced, and that dyskerin-dependent RNA pseudouridylation represents a flexible mechanism able to modulate RNA function in different ways, including modulation of splicing, change of mRNA coding properties, and selective regulation of IRES-dependent translation. We also propose a speculative model that suggests that the dynamics of pre-assembly and nuclear import of H/ACA RNPs are crucial regulatory steps that can be finely controlled in the cytoplasm in response to developmental, differentiative and stress stimuli.
MeSH term(s)	Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Dyskeratosis Congenita/genetics ; Dyskeratosis Congenita/metabolism ; Humans ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Ribonucleoproteins, Small Nucleolar/metabolism ; Telomere
Chemical Substances	Cell Cycle Proteins ; DKC1 protein, human ; Nuclear Proteins ; Ribonucleoproteins, Small Nucleolar
Language	English
Publishing date	2014-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1334659-3
ISSN	1437-4315 ; 1431-6730 ; 1432-0355
ISSN (online)	1437-4315
ISSN	1431-6730 ; 1432-0355
DOI	10.1515/hsz-2013-0287
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