Biology subjects

Schwarz, J. R.

Publications and source records attributed to Schwarz, J. R..

4 recordsLinked to original sources

bioRxiv2025

Extracellular vesicles released from cortical neurons influence spontaneous activity of recipient neurons.

Extracellular vesicles (EVs) are membranous structures that cells release into the extracellular space. EVs carry various molecules such as proteins, lipids, and nucleic acids, and serve as specialized transporters to influence other cells. In the central nervous system, EVs have been linked to many important processes, including intercellular communication, but molecular details of their physiological functions are not fully understood. Our study aimed to investigate how EVs are released by neuronal cells, and how they affect the neuronal activity of other recipient neurons. We show that mature primary cortical neurons release EVs from both their soma and dendrites. EVs released from neurons closely resemble non-neuronal EVs regarding size and marker proteins and proteomic analyses showed that neuronally released EVs contain proteins typically acting in pre- and post-synaptic compartments. Interestingly, our analysis revealed that EVs alter spontaneous activity in target neurons by increasing the amplitude of postsynaptic potentials. In summary, our findings elaborates on the role of EVs in synaptic activity modulation in neurons mediated by glutamate receptors.

neuroscience↗

bioRxiv2022

Katanin is involved in Microtubule Polymerization into Dendritic Spines and regulates Synaptic Plasticity

Dynamic microtubules transiently polymerize into dendritic spines, however intracellular factors that regulate this process and their functional role at synapses are hardly understood. Using live imaging, electrophysiology, and glutamate uncaging, we show that the microtubule-severing complex katanin is located at individual spine synapses, participates in the activity-dependent process of microtubule polymerization into dendritic spines, and regulates synaptic plasticity. Overexpression of a dominant-negative ATPase-deficient katanin subunit, did not alter microtubule growth velocities or comet density in dendrites, but significantly reduced the activity-dependent invasion of microtubules into dendritic spines. Notably, functional inhibition of katanin significantly affected the potentiation of AMPA-receptor-mediated excitatory currents after chemical induction of long-term potentiation (cLTP). Furthermore, interference with katanin function prevented structural spine remodeling following single spine glutamate uncaging. Our data identify katanin at individual spine synapses in association with PSD-95. Thus, katanin regulates postsynaptic microtubules and modulates synaptic structure and function.

neuroscience↗

bioRxiv2019

Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma

Alternative polyadenylation (APA) is a gene regulatory process that dictates mRNA 3-UTR length, resulting in changes in mRNA stability and localization. APA is frequently disrupted in cancer and promotes tumorigenesis through altered expression of oncogenes and tumor suppressors. Pan-cancer analyses have revealed common APA events across the tumor landscape; however, little is known about tumor type-specific alterations that may uncover novel events and vulnerabilities. Here we integrate RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project and The Cancer Genome Atlas (TCGA) to comprehensively analyze APA events in 148 pancreatic ductal adenocarcinomas (PDAs). We report widespread, recurrent and functionally relevant 3-UTR alterations associated with gene expression changes of known and newly identified PDA growth-promoting genes and experimentally validate the effects of these APA events on expression. We find enrichment for APA events in genes associated with known PDA pathways, loss of tumor-suppressive miRNA binding sites, and increased heterogeneity in 3-UTR forms of metabolic genes. Survival analyses reveal a subset of 3-UTR alterations that independently characterize a poor prognostic cohort among PDA patients. Finally, we identify and validate the casein kinase CK1 as an APA-regulated therapeutic target in PDA. Knockdown or pharmacological inhibition of CK1 attenuates PDA cell proliferation and clonogenic growth. Our single-cancer analysis reveals APA as an underappreciated driver of pro-tumorigenic gene expression in PDA via the loss of miRNA regulation.

cancer biology↗

bioRxiv2019

The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier

TRAAK is a membrane tension-activated K+ channel that has been associated through behavioral studies to mechanical nociception. We used specific monoclonal antibodies in mice to show that TRAAK is localized exclusively to nodes of Ranvier, the action potential propagating elements of myelinated nerve fibers. Approximately 80 percent of myelinated nerve fibers throughout the central and peripheral nervous system contain TRAAK in an all-nodes or no-nodes per axon fashion. TRAAK is not observed at the axon initial segment where action potentials are first generated. We used polyclonal antibodies, the TRAAK inhibitor RU2 and node clamp amplifiers to demonstrate the presence and functional properties of TRAAK in rat nerve fibers. TRAAK contributes to the leak K+ current in mammalian nerve fiber conduction by hyperpolarizing the resting membrane potential, thereby increasing Na+ channel availability for action potential propagation. Mechanical gating in TRAAK might serve a neuroprotective role by counteracting mechanically-induced ectopic action potentials. Alternatively, TRAAK may open in response to mechanical forces in the nodal membrane associated with depolarization during saltatory conduction and thereby contribute to repolarization of the node for subsequent spikes.

neuroscience↗