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Thomas Klarić
Genos Glycoscience Research Laboratory, Zagreb, Croatia
Numerous comparative “omics” studies have revealed unique aspects of human neurobiology, yet an evolutionary perspective of protein glycosylation in the mammalian brain is lacking. Asparagine-linked glycosylation (N-glycosylation) is a post-translational modification that is a common feature of transmembrane, secreted, and extracellular proteins and it is critically involved in many aspects of neurobiology. To gain an insight into the evolutionary trajectory of N-glycosylation in the mammalian brain, we comprehensively characterised rat, macaque, chimpanzee, and human N-glycomes from four brain regions using chromatography combined with mass spectrometry, then integrated these data with complementary glycotranscriptomic data. We found that in primates the brain N-glycome has diverged more rapidly than the underlying transcriptomic framework, providing a means for rapidly generating additional inter species diversity. We uncovered numerous phylogenetic trends in brain protein N-glycosylation as well as several human-specific adaptations. Taken together, our data suggest that brain N-glycome evolution in hominids has been characterized by an overall increase in complexity coupled with a shift in sialic acid linkage.
U. Kuliesiute1,2, R. Prokopovicius2, U. Kisieliute2, S. Kutanovas1,2, K. Merkevicius2,3, G. Luksys4,5, S. Rocka4,5 & U. Neniskyte1,2
1VU-EMBL Partnership Institute, Life Sciences Center, Vilnius University, Vilnius, Lithuania
2Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania
3Clinic of Paediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
4Centre of Neurosurgery, Vilnius University Hospital Santaros Clinics, Vilnius, Lithuania
5Department of Neurology and Neurosurgery, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
Neuronal glycocalyx has been recently recognized as an active agent that contributes to neuronal synapse formation, neuron excitability as well as neuron-autonomous and microglia-dependent brain network remodeling. In particular, the sialic acid, which often dominates the ends of the chains of glycoproteins and glycolipids on neuronal surface, is required for appropriate brain development and function. To characterize sialylation during brain development we used bioorthogonal CLICK chemistry to label de novo synthesized sialic acids in organotypic hippocampal brain slice sections. In line, by enzymatic sialidase activity measurements we demonstrated that sialylation of neurons is tightly regulated during the periods of high plasticity such as hippocampal development. Importantly, aberrant sialylation and/or desialylation are implicated in different neuropathological conditions, such as epilepsy and glioblastoma. We employed surgically resected human brain tissue and revealed that sialylation orchestrates glioblastoma tumor formation and network connectivity. Moreover, we discovered altered turnover of sialic acids and compromised enzymatic activity of sialidases in epileptic human brain tissue proposing increased sialylation of epileptic human brain. Transcriptomics of isolated epileptic and healthy human synaptosomes revealed unique molecular signatures that are found in aberrant neuronal circuitry. Altogether, our findings indicate that turnover of sialic acid as an important factor for neuronal network remodeling in brain development and circuitry diseases.
Natalia Pudełko-Malik1, Dominika Drulis-Fajdasz2, Piotr Młynarz1, Dariusz Rakus2
1Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Wroclaw, Poland
2Department of Molecular Physiology and Neurobiology, University of Wroclaw, Wroclaw, Poland
Neuronal plasticity is crucial for brain functions, but age-related changes affect it, leading to memory alterations. Current knowledge emphasizes the significant impact of Post-Translational Modifications (PTMs) like ubiquitination, glycosylation, palmitoylation, and SUMOylation on neuronal plasticity (Santos & Linder,2017). Evidence, suggests that local changes in protein localization and time-dependent activity modulations are more crucial for proper cell function than overall protein expression profiles. In our research, we concentrated on age-related changes in post-translational modifications, manifested as significant alterations in expression profiles of proteins involved in and directly executing PTMs. Our proteomic analyses identified approximately 8217 proteins for each animal group: young mice (1 month), old mice (20-22 months), and old mice treated with BAY U6751 (an inhibitor of glycogen phosphorylase (Pyg)). Our findings indicated a significant age related decrease of protein involved in common types of PTMs. But interestingly, the glycogen metabolism inhibition results in a 'rejuvenation' of the total proteome profile in old animals (Drulis-Fajdasz,2023). We observed promising trends in PTMs pathways, where e.g. de-palmitoylation and palmitoylation were significantly increased after BAY treatment, compared to old controls (p<0.05). Our data reveals significant correlations between PTMs patterns and aging, and allow to better understanding of the molecular landscape.
Miłosz Chodkowski, Andrzej Zieleziński, Savani Anbalagan
Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poznań, Poland
Studies in zebrafish can unravel the functions of cellular communication and thus identify novel bench-to-bedside drugs targeting cellular communication signaling molecules. Due to the incomplete annotation of zebrafish proteome, the knowledge of zebrafish receptors, ligands, and tools to explore their interactome is limited. To address this gap, we de novo predicted the cellular localization of zebrafish reference proteome using deep learning algorithm. We combined the predicted and existing annotations on cellular localization of zebrafish proteins and created repositories of zebrafish ligands, membrane receptome, and interactome as well as associated diseases and targeting drugs. Unlike other tools, our interactome atlas is based on both the physical interaction data of zebrafish proteome and existing human ligand-receptor pair databases. The resources are available as R and Python scripts. DanioTalk provides a novel resource for researchers interested in targeting cellular communication in zebrafish, as we demonstrate in applications studying synapse and axo-glial interactome. DanioTalk methodology can be applied to build and explore the ligand-receptor atlas of other non-mammalian model organisms.
