The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction
Abstract
Neurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain- and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active NMII light chains are colocalized with actin rings and organized in a circular periodic manner throughout the axon shaft. In contrast, NMII heavy chains are mostly positioned along the longitudinal axonal axis, being able to crosslink adjacent rings. NMII filaments can play contractile or scaffolding roles determined by their position relative to actin rings and activation state. We also show that MPS destabilization through NMII inactivation affects axonal electrophysiology, increasing action potential conduction velocity. In summary, our findings open new perspectives on axon diameter regulation, with important implications in neuronal biology.
- Authors:
-
[3];
[6];
[11];
[4];
[1]
- Nerve Regeneration Group, Porto, Portugal, i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Nerve Regeneration Group, Porto, Portugal, i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, ICBAS- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
- i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, ICBAS- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal, Neuroengineering and Computational Neuroscience Group, INEB- Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, Neuroengineering and Computational Neuroscience Group, INEB- Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- Nerve Regeneration Group, Porto, Portugal, i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, ICBAS- Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal, Neuroengineering and Computational Neuroscience Group, INEB- Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal
- Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
- i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, Chromosome Instability and Dynamics Group, Porto, Portugal
- i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal, Advanced Light Microscopy, IBMC- Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
- Stowers Institute for Medical Research, Kansas City, United States
- International Iberian Nanotechnology Laboratory, Braga, Portugal
- Advanced Light Microscopy Facility, EMBL, Heidelberg, Germany
- Publication Date:
- Sponsoring Org.:
- USDOE Office of Nuclear Energy (NE), Nuclear Fuel Cycle and Supply Chain
- OSTI Identifier:
- 1607599
- Alternate Identifier(s):
- OSTI ID: 1607600
- Grant/Contract Number:
- SFRH/BPD/114912/2016; SFRH/BD/136760/2018; PD/BD/135491/2018
- Resource Type:
- Published Article
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Name: eLife Journal Volume: 9; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Costa, Ana Rita, Sousa, Sara C., Pinto-Costa, Rita, Mateus, José C., Lopes, Cátia DF, Costa, Ana Catarina, Rosa, David, Machado, Diana, Pajuelo, Luis, Wang, Xuewei, Zhou, Feng-quan, Pereira, António J., Sampaio, Paula, Rubinstein, Boris Y., Mendes Pinto, Inês, Lampe, Marko, Aguiar, Paulo, and Sousa, Monica M. The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction. United States: N. p., 2020.
Web. doi:10.7554/eLife.55471.
Costa, Ana Rita, Sousa, Sara C., Pinto-Costa, Rita, Mateus, José C., Lopes, Cátia DF, Costa, Ana Catarina, Rosa, David, Machado, Diana, Pajuelo, Luis, Wang, Xuewei, Zhou, Feng-quan, Pereira, António J., Sampaio, Paula, Rubinstein, Boris Y., Mendes Pinto, Inês, Lampe, Marko, Aguiar, Paulo, & Sousa, Monica M. The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction. United States. https://doi.org/10.7554/eLife.55471
Costa, Ana Rita, Sousa, Sara C., Pinto-Costa, Rita, Mateus, José C., Lopes, Cátia DF, Costa, Ana Catarina, Rosa, David, Machado, Diana, Pajuelo, Luis, Wang, Xuewei, Zhou, Feng-quan, Pereira, António J., Sampaio, Paula, Rubinstein, Boris Y., Mendes Pinto, Inês, Lampe, Marko, Aguiar, Paulo, and Sousa, Monica M. Fri .
"The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction". United States. https://doi.org/10.7554/eLife.55471.
@article{osti_1607599,
title = {The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction},
author = {Costa, Ana Rita and Sousa, Sara C. and Pinto-Costa, Rita and Mateus, José C. and Lopes, Cátia DF and Costa, Ana Catarina and Rosa, David and Machado, Diana and Pajuelo, Luis and Wang, Xuewei and Zhou, Feng-quan and Pereira, António J. and Sampaio, Paula and Rubinstein, Boris Y. and Mendes Pinto, Inês and Lampe, Marko and Aguiar, Paulo and Sousa, Monica M.},
abstractNote = {Neurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain- and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active NMII light chains are colocalized with actin rings and organized in a circular periodic manner throughout the axon shaft. In contrast, NMII heavy chains are mostly positioned along the longitudinal axonal axis, being able to crosslink adjacent rings. NMII filaments can play contractile or scaffolding roles determined by their position relative to actin rings and activation state. We also show that MPS destabilization through NMII inactivation affects axonal electrophysiology, increasing action potential conduction velocity. In summary, our findings open new perspectives on axon diameter regulation, with important implications in neuronal biology.},
doi = {10.7554/eLife.55471},
journal = {eLife},
number = ,
volume = 9,
place = {United States},
year = {Fri Mar 20 00:00:00 EDT 2020},
month = {Fri Mar 20 00:00:00 EDT 2020}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.7554/eLife.55471
https://doi.org/10.7554/eLife.55471
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 33 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
The Regulation of Axon Diameter: From Axonal Circumferential Contractility to Activity-Dependent Axon Swelling
journal, September 2018
- Costa, Ana Rita; Pinto-Costa, Rita; Sousa, Sara Castro
- Frontiers in Molecular Neuroscience, Vol. 11
Actin/Myosin-V- and Activity-Dependent Inter-synaptic Vesicle Exchange in Central Neurons
journal, February 2017
- Gramlich, Michael W.; Klyachko, Vitaly A.
- Cell Reports, Vol. 18, Issue 9
Axons break in animals lacking β-spectrin
journal, January 2007
- Hammarlund, Marc; Jorgensen, Erik M.; Bastiani, Michael J.
- Journal of Cell Biology, Vol. 176, Issue 3
Sequential Treatment of SH-SY5Y Cells with Retinoic Acid and Brain-Derived Neurotrophic Factor Gives Rise to Fully Differentiated, Neurotrophic Factor-Dependent, Human Neuron-Like Cells
journal, September 2000
- Encinas, Mario; Iglesias, Montse; Liu, Yuhui
- Journal of Neurochemistry, Vol. 75, Issue 3
Determinants of conduction velocity in myelinated nerve fibers
journal, March 1980
- Waxman, Stephen G.
- Muscle & Nerve, Vol. 3, Issue 2
Dissecting Temporal and Spatial Control of Cytokinesis with a Myosin II Inhibitor
journal, March 2003
- Straight, A. F.
- Science, Vol. 299, Issue 5613
Signaling by Neuronal Swelling
journal, January 2011
- Fields, R. D.
- Science Signaling, Vol. 4, Issue 155
Coupled circumferential and axial tension driven by actin and myosin influences in vivo axon diameter
journal, October 2017
- Fan, Anthony; Tofangchi, Alireza; Kandel, Mikhail
- Scientific Reports, Vol. 7, Issue 1
Localized Myosin II Activity Regulates Assembly and Plasticity of the Axon Initial Segment
journal, February 2018
- Berger, Stephen L.; Leo-Macias, Alejandra; Yuen, Stephanie
- Neuron, Vol. 97, Issue 3
A note on conduction velocity
journal, July 1954
- Hodgkin, A. L.
- The Journal of Physiology, Vol. 125, Issue 1
Nonmuscle Myosin II Isoforms Coassemble in Living Cells
journal, May 2014
- Beach, Jordan R.; Shao, Lin; Remmert, Kirsten
- Current Biology, Vol. 24, Issue 10
Calyculin A and okadaic acid: Inhibitors of protein phosphatase activity
journal, March 1989
- Ishihara, H.; Martin, B. L.; Brautigan, D. L.
- Biochemical and Biophysical Research Communications, Vol. 159, Issue 3
Irregular geometries in normal unmyelinated axons: A 3D serial EM analysis
journal, December 1990
- Greenberg, M. M.; Leitao, C.; Trogadis, J.
- Journal of Neurocytology, Vol. 19, Issue 6
Myosin II has distinct functions in PNS and CNS myelin sheath formation
journal, September 2008
- Wang, Haibo; Tewari, Ambika; Einheber, Steven
- Journal of Cell Biology, Vol. 182, Issue 6
Interfacing Microfluidics with Microelectrode Arrays for Studying Neuronal Communication and Axonal Signal Propagation
journal, January 2018
- Lopes, Cátia D. F.; Mateus, José C.; Aguiar, Paulo
- Journal of Visualized Experiments, Issue 142
Culturing hippocampal neurons
journal, December 2006
- Kaech, Stefanie; Banker, Gary
- Nature Protocols, Vol. 1, Issue 5
Myosin phosphatase target subunit: Many roles in cell function
journal, April 2008
- Matsumura, Fumio; Hartshorne, David J.
- Biochemical and Biophysical Research Communications, Vol. 369, Issue 1
The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap
journal, June 2015
- Brown, Jeffrey W.; Bullitt, Esther; Sriswasdi, Sira
- PLOS Computational Biology, Vol. 11, Issue 6
Characterization of Three Full-length Human Nonmuscle Myosin II Paralogs
journal, September 2013
- Billington, Neil; Wang, Aibing; Mao, Jian
- Journal of Biological Chemistry, Vol. 288, Issue 46
Actin, Spectrin, and Associated Proteins Form a Periodic Cytoskeletal Structure in Axons
journal, December 2012
- Xu, K.; Zhong, G.; Zhuang, X.
- Science, Vol. 339, Issue 6118
Subdiffraction-Resolution Fluorescence Imaging with Conventional Fluorescent Probes
journal, August 2008
- Heilemann, Mike; van de Linde, Sebastian; Schüttpelz, Mark
- Angewandte Chemie International Edition, Vol. 47, Issue 33
Ultrastructure of the axonal periodic scaffold reveals a braid-like organization of actin rings
journal, December 2019
- Vassilopoulos, Stéphane; Gibaud, Solène; Jimenez, Angélique
- Nature Communications, Vol. 10, Issue 1
Myosin IIA Heavy Chain Phosphorylation Mediates Adhesion Maturation and Protrusion in Three Dimensions
journal, January 2017
- Rai, Vandana; Thomas, Dustin G.; Beach, Jordan R.
- Journal of Biological Chemistry, Vol. 292, Issue 8
Fluorescence nanoscopy by ground-state depletion and single-molecule return
journal, September 2008
- Fölling, Jonas; Bossi, Mariano; Bock, Hannes
- Nature Methods, Vol. 5, Issue 11
A major role for the Rho-associated coiled coil forming protein kinase in G-protein-mediated Ca 2+ sensitization through inhibition of myosin phosphatase in rabbit trachea
journal, October 1999
- Iizuka, Kunihiko; Yoshii, Akihiro; Samizo, Koichi
- British Journal of Pharmacology, Vol. 128, Issue 4
A Myosin V Inhibitor Based on Privileged Chemical Scaffolds
journal, September 2010
- Islam, Kabirul; Chin, Harvey F.; Olivares, Adrian O.
- Angewandte Chemie International Edition, Vol. 49, Issue 45
Non-muscle myosin II takes centre stage in cell adhesion and migration
journal, November 2009
- Vicente-Manzanares, Miguel; Ma, Xuefei; Adelstein, Robert S.
- Nature Reviews Molecular Cell Biology, Vol. 10, Issue 11
µSpikeHunter: An advanced computational tool for the analysis of neuronal communication and action potential propagation in microfluidic platforms
journal, April 2019
- Heiney, Kristine; Mateus, José C.; Lopes, Cátia D. F.
- Scientific Reports, Vol. 9, Issue 1
The Actin-Binding Protein α-Adducin Is Required for Maintaining Axon Diameter
journal, April 2016
- Leite, Sérgio Carvalho; Sampaio, Paula; Sousa, Vera Filipe
- Cell Reports, Vol. 15, Issue 3