Biology subjects

Mosbacher, J.

Publications and source records attributed to Mosbacher, J..

3 recordsLinked to original sources

bioRxiv2026

Local translation drives glioblastoma heterogeneity and tumor invasion

O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/722387v1_ufig1.gif" ALT="Figure 1"> View larger version (96K): org.highwire.dtl.DTLVardef@1da020corg.highwire.dtl.DTLVardef@1bc9b32org.highwire.dtl.DTLVardef@171198aorg.highwire.dtl.DTLVardef@43ce6f_HPS_FORMAT_FIGEXP M_FIG C_FIG Glioblastoma is characterized by diffuse brain invasion, yet the subcellular mechanisms enabling this aggressive behavior remain poorly understood. A subpopulation of glioblastoma cells forms invasive tumor microtubes (TMs), neurite-like extensions that drive whole-brain colonization. Here, we establish local protein translation as a fundamental driver of TM dynamics and invasive cell states. Developing a subcellular transcriptomics approach - integrating subcellular organelle organization with spatially resolved transcriptomics and functional readouts - we reveal that TM gene expression drives cell state identity. Invasive cells further exhibit significantly elevated local translation in protruding TMs, directly linking subcellular protein synthesis to functional invasive states associated with neurodevelopmental programs of axonal growth cones. Targeted disruption of TM-localized translation via photoswitchable puromycin, and specific knockdowns of the TM-enriched proteins GPM6A and GAP43, impaired TM dynamics, suppressed invasion, and reduced tumor growth. Together, these findings define local translation as a key determinant of tumor heterogeneity and glioblastoma invasion.

cancer biology↗

bioRxiv2025

Brain-wide synaptosome profiling reveals localized mRNAs that diversify synapses

Chemical synapses are the principal communication nodes of the brain, defined by their specialization and plasticity. Their diversity spans multiple levels, from the polarity and magnitude of electrophysiological responses to the proteins driving these differences. Here, we describe another layer of synapse diversity - synaptic transcriptome diversity. Using transgenic mice to fluorescently label presynapses in Camk2a-, Gad2-, DAT-, PV-, SST-, and VIP-expressing neurons, combined with fluorescence-activated synaptosome sorting, we profiled synaptic transcriptomes across five brain regions. We identified [~]4000 mRNAs enriched at synapses - some type-specific, others shared - and highlight region-specific enrichments of mRNAs encoding protein subunits or family members. We found that the abundance of synaptic mRNAs is not a passive reflection of their abundance in cellular somata, indicating active trafficking and sorting mechanisms. Integrating transcriptomic and proteomic data, we identified [~]90 genes with significantly correlated mRNA-protein ratios across regions, mainly involved in synaptic vesicle dynamics, receptor signaling, and calcium regulation, suggesting a key role for local translation in maintaining protein copy number. Although synaptic mRNAs represent only a fraction of the templates for the synaptic proteome, the synaptic transcriptome reflects the synapse diversity captured by the proteome equally well. Together, this dataset (https://syndive.org/) provides a resource for exploring how synaptic mRNA localization and local translation shape synaptic identity and function.

neuroscience↗

bioRxiv2024

The molecular diversity of hippocampal regions and strata at synaptic resolution revealed by integrated transcriptomic and proteomic profiling

The molecular diversity of neurons and their synapses underlies the different responses and plasticity profiles that drive all neural circuits and behavior. While the extent of this diversity has been partially revealed by transcriptomic and proteomic profiling, combined studies of neuronal transcripts and proteins are limited. Here, we used microdissection of mouse hippocampal subregions and CA1 strata and fluorescence-activated synaptosome sorting (FASS) to characterize the transcripts and proteins from different hippocampal neurons and their compartments with synaptic resolution. Parallel RNA-seq and LC-MS/MS of microdissections identified over 15,000 mRNA transcripts and 10,000 proteins, revealing thousands with local enrichment such as classes of glutamate receptors and voltage-gated potassium channels, myelin-associated molecules, and adhesion molecules. Synaptosome analysis further identified specific enrichment of molecules from collagen, ribosome, solute carrier, and receptor families at different synapses formed along CA1 neurons. By integrating mRNA and protein data, we defined clusters of co-regulated molecules such as adhesion and neurofilament proteins and transporter mRNAs, and found subsets of mRNA-protein pairs with strong correlation and anti-correlation in their abundance variation. Our findings comprise a rich resource on the molecular landscape of the hippocampus and its synapses that is accessible at syndive.org, and highlight the coordinated organization of transcripts and proteins between regions, neuronal compartments, and synapses.

neuroscience↗