Transporting cargo over long distance: insights from dynein/dynactin structures by Andrew Carter

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 Collective Dynamics of-, on- and around Filaments in Living Cells: Motors, Maps, Tips and Tracks
0:00:08 Transporting cargo over long distance: insights from dynein/dynactin structures
0:01:30 Cytoplasmic dynein has many cargoes
0:02:37 Dynein is linked to diseases
0:04:41 Dynein functions as a large complex
0:06:03 Dynactin is built round an actin-like filament
0:10:13 Cryo-EM structures of dynactin
0:11:09 Cryo-EM reveals rare conformations
0:11:55 Structural model of the dynactin complex
0:13:40 The shoulder is dynactin's molecular ruler
0:15:18 How does dynein bind dynactin?
0:16:33 Dynein and BICD2 bind to the dynactin filament
0:17:48 The dynein-dynactin transport machine
0:19:07 Dynactin/BICD2 activate dynein
0:20:07 How is dynein alone inhibited?
0:21:06 The structure of human dynein-1 in the Phi conformation.
0:22:43 The interface between motor domains in the phi-particle
0:24:08 Breaking apart the phi-particle is not sufficient to activate dynein
0:25:29 Dynactin flips dynein's motor domains so they are parallel
0:26:54 Dynein activation: dynactin flips the motor domains so both can bind the microtubule
0:30:34 Disrupting the phi-particle causes dynein mislocalization in cells
0:31:52 A multistep pathway for dynein activation
0:32:16 How do different adaptors bind dynein/dynactin?
0:33:55 Adaptors link dynein to different cargoes
0:34:25 Many adaptors contain coiled-coils
0:35:48 Hook3 and BICDR1 recruit two dyneins
0:36:52 Adaptors could increase speed by reducing backwards and sideways steps
0:38:09 BICD2 is biased toward recruiting 1 dynein BICDR1 and HOOK recruit 2
0:38:55 Hook3 and BICDR1 complexes move faster
0:40:57 How is the second dynein recruited?
0:42:00 Focused classification and refinement of flexible regions
0:42:29 High resolution structure of dynein tail
0:43:02 Intermediate chain binding to HC
0:43:20 Terminal helices staple to the LIC to the HC
0:43:42 Accommodation of the second dynein
0:45:36 The dynein/dynactin transport machine
0:46:03 Acknowledgements
0:46:26 Q&A
0:49:19 Can BICD2 binding two dyneins?
0:54:46 Hook3 and BICDR complexes produce more force than BICD2 complexes