Cargo crowding at actin-rich regions causes traffic jams in neurons by Sandhya P Koushika

Collective Dynamics of-, on- and around Filaments in Living Cells: Motors, MAPs, TIPs and Tracks DATE: 28 October 2017 to 02 November 2017 VENUE: Ramanujan Lecture Hall, ICTS Bangalore Our knowledge of cytoskeletal filaments, nucleic acid filaments (DNA and RNA) as well as their associated proteins is constantly expanding due to application of a range of recent biophysical techniques which has helped scientists to probe biophysical phenomena at molecular, cellular and tissue levels. Cytoskeletal filaments, particularly microtubules (MT) and filamentous actin (F-actin), not only provide mechanical strength to an eukaryotic cell but also form a fibrous network that serves at the network of tracks for transporation system of the cell. The dynamics of these filaments and the mechanisms of force generation by polymerization/depolymerization have been investigated experimentally as well as theoretically at multiple scales. Nucleic acid strands (DNA/RNA) are more flexible filaments. The hierarchical organization and dynamics of both cytoskeletal and nucleic acid filaments depend crucially on the proteins bound to these filaments. Cytoskeletal motor proteins utilize the respective cytoskeletal filamentous tracks for directed, albeit noisy, movements that result in intracellular motility and/or contractility. The power and efficiency of these motors have been under intense investigation over the last two decades. Although most of the physical principles involved in the energy transduction and motility of the cytoskeletal motors and NA-based motors are common, most often these are investigated by two distinct communities of investigators, hence limited interaction between them. Exchange of ideas and methodologies between these two communities is likely to enrich both these areas of research. The main focus of this Discussion Meeting is to bring leading practitioners from both these areas on a single forum thereby catalyzing progress in both by comparing and contrasting the main conceptual challenges in these two areas. Sessions will be organized based on common underlying principles for cytoskeletal motors and NA-based motors looking at sub-, single- and multi-machine level. There will be 20 hours of lectures over the course of the meeting and the rest of the time will be reserved for interactions and discussions. CONTACT US: [email protected] PROGRAM LINK: https://www.icts.res.in/discussion-me... Table of Contents (powered by https://videoken.com) 0:00:00 Start 0:00:07 Cargo crowding at actin-rich regions causes traffic jams in neurons 0:00:26 Axonal transport is an essential process 0:01:49 The journey of an individual cargo vesicle is a multi-step process 0:02:30 How do you maintain cargo flux in an axon? 0:04:39 Cargo move in cytoskeletally-rich environments in axons 0:05:23 Many obstacles in the path 0:05:52 Transport path may be narrow 0:06:23 Neuronal highway is not homogeneous 0:07:48 Synaptic vesicle transport in vivo 0:08:44 Typical movements and stationary cargo 0:09:48 All cargo examined are stationary for long periods of time 0:10:27 Do different cargo pile up together? 0:11:00 Multiple cargo types are stationary at the same locations 0:11:42 Where do cargo pile up? 0:12:31 Imaging to identify locations where cargo halt 0:12:54 Stationary cargo are at actin-rich regions 0:13:53 Reducing actin-rich regions alters stationary cargo density 0:14:25 Reducing actin-rich regions increases fraction of moving cargo 0:14:43 What do moving cargo do when encountering a stalled cargo? 0:15:37 Cargo halt predominantly where other cargo are present 0:16:03 Cargo crowding induces traffic jams 0:19:36 Cargo stop at crowded regions 0:20:36 Locations where cargo become stationary regulate local flux 0:21:29 How far a vesicle moves depends on density of stationary vesicles 0:22:03 Physical crowding leads to stalling 0:26:43 Are there ways to overcome traffic 0:27:18 Change in motion state is essential to go bypass traffic jams 0:29:20 Reversals occur through out the neuron 0:32:06 Cargo reverse through out the axon 0:33:43 Are naturally occurring pools of vesicles physiologically relevant? 0:34:33 The gentle touch assay 0:35:17 Density of stationary pre-SVs reduce after stimulation 0:35:51 Density of stationary pre-SVs after stimulation 0:37:34 Conclusion 0:40:09 Credits-students/post-docs 0:40:32 Q&A