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Special Issue "Transglutaminase 2 and Cellular Functions"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 June 2023 | Viewed by 344

Special Issue Editors

Special Issue Information

Dear Colleagues,

Transglutaminase type 2 (TG2) is a calcium-dependent enzyme, ubiquitously expressed belonging to the transglutaminase family (EC TG2 catalyzes specific post-translational modifications of proteins through a transamidation reaction. It is also involved in various additional enzymatic activities, such as guanine nucleotide binding and hydrolysis, protein kinase, and disulfide isomerase activities.

TG2 is a widely studied enzyme and the greater the understanding of it the more new implications emerge. Since 2000, over 2400 papers have demonstrated that TG2 plays a central role in several biological mechanisms and cellular functions, such as cell proliferation, apoptosis, and differentiation in various cell types. The protein itself as well as its enzymatic activity are determining factors for the proliferation and invasion of tumor cells, and for the response of the tumor to chemotherapy. It was implicated in a growing variety of altered health states, not just celiac disease, but also neurodegenerative diseases, multiple sclerosis, and central nervous system injuries, among others.

The knowledge of the mechanisms through which TG2 participates in the various cellular functions, in particular those that trigger apoptosis or pathogenesis, could allow the design of future therapeutic applications. In this regard, the study of the biological effects of modulating molecules of the enzymatic activity of TG2 and/or of the effectors that are part of the cascade of events triggered arouses enormous interest. For example, biogenic polyamines, which act as natural substrates, have been shown to limit, and in some cases block, the enzymatic activity of TG2, resulting in possible use to reduce the onset of pathologies, such as senile cataracts.

Based on these premises, this monograph aims to broaden the knowledge of TG2 in health conditions and pathological states and the cellular functions in which it is involved. Studies that clarify the molecular mechanisms triggered by TG2, and also those focused on the identification of possible natural or synthetic modulators of the TG2 activity, are particularly welcome.

You may choose our Joint Special Issue in Medical Sciences.

Prof. Dr. Carlo Mischiati
Prof. Dr. Simone Beninati
Guest Editors

Manuscript Submission Information

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Published Papers (1 paper)

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Deletion of Transglutaminase 2 from Mouse Astrocytes Significantly Improves Their Ability to Promote Neurite Outgrowth on an Inhibitory Matrix
Int. J. Mol. Sci. 2023, 24(7), 6058; https://doi.org/10.3390/ijms24076058 - 23 Mar 2023
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Astrocytes are the primary support cells of the central nervous system (CNS) that help maintain the energetic requirements and homeostatic environment of neurons. CNS injury causes astrocytes to take on reactive phenotypes with an altered overall function that can range from supportive to [...] Read more.
Astrocytes are the primary support cells of the central nervous system (CNS) that help maintain the energetic requirements and homeostatic environment of neurons. CNS injury causes astrocytes to take on reactive phenotypes with an altered overall function that can range from supportive to harmful for recovering neurons. The characterization of reactive astrocyte populations is a rapidly developing field, and the underlying factors and signaling pathways governing which type of reactive phenotype that astrocytes take on are poorly understood. Our previous studies suggest that transglutaminase 2 (TG2) has an important role in determining the astrocytic response to injury. Selectively deleting TG2 from astrocytes improves functional outcomes after CNS injury and causes widespread changes in gene regulation, which is associated with its nuclear localization. To begin to understand how TG2 impacts astrocytic function, we used a neuron-astrocyte co-culture paradigm to compare the effects of TG2−/− and wild-type (WT) mouse astrocytes on neurite outgrowth and synapse formation. Neurons were grown on a control substrate or an injury-simulating matrix comprised of inhibitory chondroitin sulfate proteoglycans (CSPGs). Compared to WT astrocytes, TG2−/− astrocytes supported neurite outgrowth to a significantly greater extent only on the CSPG matrix, while synapse formation assays showed mixed results depending on the pre- and post-synaptic markers analyzed. We hypothesize that TG2 regulates the supportive functions of astrocytes in injury conditions by modulating gene expression through interactions with transcription factors and transcription complexes. Based on the results of a previous yeast two-hybrid screen for TG2 interactors, we further investigated the interaction of TG2 with Zbtb7a, a ubiquitously expressed transcription factor. Co-immunoprecipitation and colocalization analyses confirmed the interaction of TG2 and Zbtb7a in the nucleus of astrocytes. Overexpression or knockdown of Zbtb7a levels in WT and TG2−/− astrocytes revealed that Zbtb7a robustly influenced astrocytic morphology and the ability of astrocytes to support neuronal outgrowth, which was significantly modulated by the presence of TG2. These findings support our hypothesis that astrocytic TG2 acts as a transcriptional regulator to influence astrocytic function, with greater influence under injury conditions that increase its expression, and Zbtb7a likely contributes to the overall effects observed with astrocytic TG2 deletion. Full article
(This article belongs to the Special Issue Transglutaminase 2 and Cellular Functions)
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