Dudko, O. | Search bioRxiv

bioRxiv2020

A Theory of Synaptic Transmission

Rapid and precise neuronal communication is enabled through a highly synchronous release of signaling molecules neurotransmitters into the synaptic cleft within just milliseconds of the action potential. Yet neurotransmitter release lacks a theoretical framework that is both phenomenologically accurate and mechanistically realistic. Here, we formulate an analytic theory of the action-potential-triggered neurotransmitter release at a chemical synapse. The theory captures general principles of synaptic transmission while generating concrete predictions for particular synapses. A universal scaling in synaptic transmission is established, and demonstrated through a collapse of experimental data from different synapses onto a universal curve. The theory shows how key characteristics of synaptic function - plasticity, fidelity, and efficacy - emerge from molecular mechanisms of neurotransmitter release machinery.

biophysics↗

bioRxiv2018

Antigen receptor locus dynamics is orchestrated near the sol-gel phase transition to enforce stepwise VDJ gene rearrangement

Diverse antibody repertoires are generated through remote genomic interactions involving immunoglobulin variable (VH), diversity (DH) and joining (JH) gene segments. How such interactions are orchestrated remains unknown. We developed a novel strategy to track VH-DHJH motion and interactions in live B-lymphocytes. We found that VH and DHJH segments were trapped in configurations that only allowed constrained local motion, such that spatially proximal VH and DHJH segments remained in proximity, whereas spatially remote segments explored their immediate neighborhood while remaining remote. Comparison of experimental and simulated data revealed that such a highly constrained motion was imposed by a network of cross-linked chromatin chains characteristic of a gel phase, yet it was poised near the sol phase, a solution of independent chromatin chains. We propose that epigenetically induced gel droplets and the proximity to the sol-gel phase transition constitute the mechanism that orchestrates ordered VDJ rearrangement.

immunology↗