Biology subjects

Monteggia, L. M.

Publications and source records attributed to Monteggia, L. M..

3 recordsLinked to original sources

bioRxiv2026

Regulation of tumor proliferation by unlocking silent synapses on metastatic cancer cells

Several studies have revealed deleterious synapse formation onto cancer cells within the brain tumor microenvironment, yet these synapses are [~]100-fold weaker in presynaptic release rates and postsynaptic strength relative to bona fide synapses formed between neurons. Here, we find that most of the functional synapses on tumor cells are kept dormant and can be unlocked by overcoming GABAB receptor-mediated metabotropic signaling in neurons. Scavenging G{beta}{gamma} signaling in neurons increased presynaptic release probability on tumor cells and augmented cancer cell proliferation. Optical analysis of the tumor microenvironment revealed regulated secretion of neurotransmitters from tumor cells in response to GABAB receptor inhibition or electrical stimulation. These results reveal how cancer cells with a high propensity for brain metastasis leverage precise moments of aberrant excitation between neurons to engage reciprocal interactions that ultimately fuel cancer proliferation.

neuroscience↗

bioRxiv2021

Probing the segregation of evoked and spontaneous neurotransmission via photobleaching and recovery of a fluorescent glutamate sensor

Synapses maintain both action potential-evoked and spontaneous neurotransmitter release, however, organization of these two forms of release within an individual synapse remains unclear. Here, we used photobleaching properties of iGluSnFR, a fluorescent probe that detects glutamate, to investigate the subsynaptic organization of evoked and spontaneous release. In non-neuronal cells and neuronal dendrites, iGluSnFR fluorescence is intensely photobleached and recovers via diffusion of non-photobleached probes within 10-seconds. After photobleaching, while evoked iGluSnFR events could be rapidly suppressed, their recovery required several hours. In contrast, iGluSnFR responses to spontaneous release were comparatively resilient to photobleaching, unless the complete pool of iGluSnFR was activated by glutamate perfusion. This differential effect of photobleaching on different modes of neurotransmission is consistent with a subsynaptic organization where sites of evoked glutamate release are clustered and corresponding iGluSnFR probes are diffusion restricted, while spontaneous release sites are broadly spread across a synapse with readily diffusible iGluSnFR probes.

neuroscience↗

bioRxiv2020

Persistence of quantal synaptic vesicle recycling following dynamin depletion

Dynamins are GTPases required for pinching vesicles off the plasma membrane once a critical curvature is reached during endocytosis. Here, we probed dynamin function in central synapses by depleting all three dynamin isoforms in postnatal hippocampal neurons. We found a decrease in the propensity of evoked neurotransmission as well as a reduction in synaptic vesicle numbers. Using the fluorescent reporter vGluT1-pHluorin, we observed that compensatory endocytosis after 20 Hz stimulation was arrested in ~40% of presynaptic boutons, while remaining synapses showed only a modest effect suggesting the existence of a dynamin-independent endocytic pathway in central synapses. Surprisingly, we found that the retrieval of single synaptic vesicles, after either evoked or spontaneous fusion, was largely impervious to disruption of dynamins. Overall, our results suggest that classical dynamin-dependent endocytosis is not essential for retrieval of synaptic vesicle proteins after quantal single synaptic vesicle fusion.

neuroscience↗