Biology subjects

Dresselhaus, E. C.

Publications and source records attributed to Dresselhaus, E. C..

4 recordsLinked to original sources

bioRxiv2026

Distinct Rab11-associated membrane trafficking pathways bidirectionally control neuronal extracellular vesicle cargo traffic

Neuronal extracellular vesicles (EVs) are released from synapses, and play roles in cellular communication, proteostasis, and the spread of toxic proteins in disease. The small GTPase Rab11 is required to maintain a reservoir of EV cargoes at presynaptic terminals, but how its diverse effector proteins contribute to this function and where Rab11 acts in neurons remains unclear. Using Drosophila motor neurons as a model, we show that EV cargoes redistribute from synapses to axons and cell bodies in rab11 mutants, concomitant with reduced release from synapses. We conducted a directed genetic screen of Rab11-associated factors and found that they have distinct roles in EV trafficking. Tethering and sorting factors are required to maintain levels of presynaptic EV precursors, supporting the hypothesis that Rab11 regulates EV cargo pools through recycling flux rather than by directly mediating EV release. Unexpectedly, we found that different classes of Rab11-associated proteins have opposite functions: the motor protein MyoV and the PI4KIII component Rbo sustain cargo levels at synapses, while the motor adaptor Nuf/Rab11FIP4 and the PI4KIII{beta} homolog Fwd restrict cargo levels. Together, these results indicate that Rab11 regulates multiple distinct organelle transport trajectories and PI(4)P populations to direct EV cargoes toward different cellular fates.

cell biology↗

bioRxiv2025

Cycling Molecular Assemblies (CyMA) for Ultrasensitive Golgi Imaging

The Golgi apparatus is central to intracellular trafficking, yet its dynamic visualization remains constrained by probes that require high concentrations and long incubations. Here we present cycling molecular assemblies (CyMA), a design concept that harnesses endogenous dynamic enzymatic futile cycle to drive ultrasensitive imaging. The BODIPY-CyMA probe operates through reversible palmitoylation-depalmitoylation mediated by palmitoyl acyltransferases and thioesterases, establishing a nonequilibrium steady-state that actively concentrates the probe at the Golgi. This enzymatic cycling converts diffusion-limited localization into self-amplifying signal generation, enabling morphology imaging at concentrations as low as 100 pM and real-time tracking of Golgi dynamics within minutes at nanomolar levels. This probe requires minimal incubation time, exhibits negligible cytotoxicity, faithfully reports pharmacological Golgi disassembly, and functions in vivo in Drosophila larvae. BODIPY-CyMA exemplifies how coupling molecular self-assembly to endogenous enzymatic cycles affords a general strategy for constructing dynamic, non-perturbative probes for live cell and in vivo imaging.

biochemistry↗

bioRxiv2023

ESCRT disruption provides evidence against signaling functions for synaptic exosomes

Extracellular vesicles (EVs) are released by many cell types including neurons, carrying cargoes involved in signaling and disease. It is unclear whether EVs promote intercellular signaling or serve primarily to dispose of unwanted materials. We show that loss of multivesicular endosome-generating ESCRT (endosomal sorting complex required for transport) machinery disrupts release of EV cargoes from Drosophila motor neurons. Surprisingly, ESCRT depletion does not affect the signaling activities of the EV cargo Synaptotagmin-4 (Syt4) and disrupts only some signaling activities of the EV cargo Evenness Interrupted (Evi). Thus, these cargoes may not require intercellular transfer via EVs, and instead may be conventionally secreted or function cell autonomously in the neuron. We find that EVs are phagocytosed by glia and muscles, and that ESCRT disruption causes compensatory autophagy in presynaptic neurons, suggesting that EVs are one of several redundant mechanisms to remove cargoes from synapses. Our results suggest that synaptic EV release serves primarily as a proteostatic mechanism for certain cargoes.

cell biology↗

bioRxiv2018

Targeting of NF-κB to Dendritic Spines is Required for Synaptic Signaling and Spine Development

Long-term forms of brain plasticity share a requirement for changes in gene expression induced by neuronal activity. Mechanisms that determine how the distinct and overlapping functions of multiple activity-responsive transcription factors, including nuclear factor kappa B (NF-{kappa}B), give rise to stimulus-appropriate neuronal responses remain unclear. We report that the p65/RelA subunit of NF-{kappa}B confers subcellular enrichment at neuronal dendritic spines and engineer a p65 mutant that lacks spine-enrichment ({Delta}SEp65) but retains inherent transcriptional activity equivalent to wild-type p65. Wild-type p65 or {Delta}SEp65 both rescue NF-{kappa}B-dependent gene expression in p65-deficient murine hippocampal neurons responding to diffuse (PMA/ionomycin) stimulation. In contrast, neurons lacking spine-enriched NF-{kappa}B are selectively impaired in NF-{kappa}B-dependent gene expression induced by elevated excitatory synaptic stimulation (bicuculline or glycine). We used the setting of excitatory synaptic activity during development that produces NF-{kappa}B-dependent growth of dendritic spines to test physiological function of spine-enriched NF-{kappa}B in an activity-dependent response. Expression of wild-type p65, but not {Delta}SEp65, is capable of rescuing spine density to normal levels in p65-deficient pyramidal neurons. Collectively, these data reveal that spatial localization in dendritic spines contributes unique capacities to the NF-{kappa}B transcription factor in synaptic activity-dependent responses.\n\nSIGNIFICANCE STATEMENTExtensive research has established a model in which the regulation of neuronal gene expression enables enduring forms of plasticity and learning. However, mechanisms imparting stimulus-specificity to gene regulation, insuring biologically appropriate responses, remain incompletely understood. NF-{kappa}B is a potent transcription factor with evolutionarily-conserved functions in learning and the growth of excitatory synaptic contacts. Neuronal NF-{kappa}B is localized in both synapse and somatic compartments, but whether the synaptic pool of NF-{kappa}B has discrete functions is unknown. This study reveals that NF-{kappa}B enriched in dendritic spines (the postsynaptic sites of excitatory contacts) is selectively required for NF-{kappa}B activation by synaptic stimulation and normal dendritic spine development. These results support spatial localization at synapses as a key variable mediating selective stimulus-response coupling.

neuroscience↗