Close

Actomyosin-II facilitates long-range retrograde transport of large cargoes by controlling axonal radial contractility

Tong Wang, Wei Li, Sally Martin, Andreas Papadopulos, Golnoosh Shamsollahi, Vanessa Lanoue, Pranesh Padmanabhan, He Huang, Xiaojun Yu, Victor Anggono, Frederic Meunier

Preprint posted on 13 December 2018 https://www.biorxiv.org/content/early/2018/12/13/492959

Article now published in Journal of Cell Biology at http://dx.doi.org/10.1083/jcb.201902001

Be flexible or die: how neuronal axons transport large cargos.

Selected by Ivana Viktorinová

Categories: cell biology, neuroscience

Introduction

In this preprint, the authors address the mechanism which underlies cargo transport in neurons. Neurons are highly polarized cells that comprise of a cell body (a dendrite) and a long and thin axon. It is known that cargo can be transported in a bidirectional (anterograde and retrograde) manner in the terminal of the axon and retrograde within the axonal shaft. Interestingly, the transported cargo can be larger than the diameter of the axon. For example, human corpus callosum axons reach a diameter of ca. 0.64-0.74 µm whilst transported autophagosomes can be almost 1.5 µm, mitochondria up to 3 µm and endosomes up to 1 µm in diameter. Therefore, the authors hypothesize that there must be radial contractility in axons that allows transient expansion to transport such large cargo.

Findings

The authors combine super-resolution microscopy, electron and confocal microscopy to image fixed and live rat hippocampal neurons labeled with selected dyes, transfected with fluorescently-tagged constructs or NM-II antibodies. The authors find that:

1) The speed of cargo transportation inversely correlates with cargo size.

2) The axons undergo dynamic local deformation during the transportation of larger cargo, as the diameter is enlarged to allow the cargo to pass through and then immediately constricted afterwards.

3) This transient change in axon diameter is mediated by NM-II.

4) NM-II forms a ~ 200 nm periodic structure that is placed perpendicular to the longitudinal axon axis, similar to the F-actin ring MPS. It is a pity that the authors could not find a clear co-localization pattern between NM II and F-actin MPS. However, their further experiments seem to support that NM-II correlates with actin MPS. Thus, the authors conclude that NM-II controls the contraction of the subcortical actin MPS and this actomyosin MPS underlies the radial contractility of axons.

Co-localization of actomyosin MPS and their position relatively to the longitudinal axis of the axon.
  • Question: Would the transfection with the phospho-MRLC or MRLC-GFP construct help to elucidate the colocalization issue? The authors transfected hippocampal neurons with the MRLC-GFP construct later in the manuscript.

5) Next, the authors asked whether the radial contraction of axons could play a role in cargo transport. Using blebbistatin, which affects NM-II function, for 60 mins they find that axons dilate. This is followed by an initial increase of the speed for retrograde moving large cargos, which then stalls in a back-and-forth state. Interestingly, the speed of small cargo transportation is not affected. Looking at the large cargo in detail, they also identify that overall efficacy of the cargo transport is actually reduced. This leads them into a conclusion that radial axonal contractility is required for correct long-range retrograde cargo transport and their directionality in neurons.

  • Question: The explanation in this preprint as to why large cargoes initially travel quickly and then end up in a back-and-forth state after 60 min of blebbistatin treatment seems to me interesting. However, why is the large cargo not moving at least slowly after the blebbistatin treatment (axon dilatation) when dynein and microtubules are not affected within 60 mins? Is dynein-supported transportation limited to a certain cargo size? 
6) Long blebbistatin treatment (60-120 mins) results in focal axon swelling (FAS) and an axonal degeneration-like state. The authors also show that transfection with the mutant MRLC-GFP construct leads to a similar axonal damage.
  • Question: What do dynein and microtubules look like then in these long-time blebbistatin treated axons and in those transfected with the MRLC-GFP mutant construct? If affected, do you think that NM-II defines/regulates microtubules (axonal structure) in these neurons? 
  • Further questions: Coming from the planar cell polarity field, does the size spacing (~ 200 nm)/regularity of actomyosin MPS have a function in pushing large cargoes? Have you tried a transfection with polarity mutant constructs that disrupt this regular MPS distribution (or cargo transport)?

Summary

The authors conclude that CNS axons are under constitutive radial constriction/contractility, which limits their diameter and supports effectively unidirectional retrograde cargo transport (to the neuron body). In turn, this contributes to the survival and healthy function of neurons. 

Why I chose it

I find it cool that it is possible to simply culture rat neurons in a dish and observe how they transport stained cargo. I like the article as it is well written and easy to understand. Although many experiments are performed here, this preprint is focused, simple and clean.

 

Tags: actomyosin, axon, cargo transport, contractility, degeneration, hippocampal, large cargoes, neuron, rat, retrograde transport

Posted on: 15 January 2019 , updated on: 16 January 2019

doi: https://doi.org/10.1242/prelights.7272

Read preprint (No Ratings Yet)

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the cell biology category:

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

BioMalPar XVI: Biology and Pathology of the Malaria Parasite

[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria

 



List by Dey Lab, Samantha Seah

1

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

 



List by Pablo Ranea Robles

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

MitoList

This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.

 



List by Sandra Franco Iborra

Biophysical Society Annual Meeting 2019

Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA

 



List by Joseph Jose Thottacherry

ASCB/EMBO Annual Meeting 2018

This list relates to preprints that were discussed at the recent ASCB conference.

 



List by Dey Lab, Amanda Haage

Also in the neuroscience category:

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.

 



List by Alex Eve

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London

 



List by Alex Eve
Close