Cargando…

Modeling of the axon plasma membrane structure and its effects on protein diffusion

The axon plasma membrane consists of the membrane skeleton, which comprises ring-like actin filaments connected to each other by spectrin tetramers, and the lipid bilayer, which is tethered to the skeleton via, at least, ankyrin. Currently it is unknown whether this unique axon plasma membrane skele...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yihao, Tzingounis, Anastasios V., Lykotrafitis, George
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497228/
https://www.ncbi.nlm.nih.gov/pubmed/31048841
http://dx.doi.org/10.1371/journal.pcbi.1007003
_version_ 1783415430838222848
author Zhang, Yihao
Tzingounis, Anastasios V.
Lykotrafitis, George
author_facet Zhang, Yihao
Tzingounis, Anastasios V.
Lykotrafitis, George
author_sort Zhang, Yihao
collection PubMed
description The axon plasma membrane consists of the membrane skeleton, which comprises ring-like actin filaments connected to each other by spectrin tetramers, and the lipid bilayer, which is tethered to the skeleton via, at least, ankyrin. Currently it is unknown whether this unique axon plasma membrane skeleton (APMS) sets the diffusion rules of lipids and proteins in the axon. To answer this question, we developed a coarse-grain molecular dynamics model for the axon that includes the APMS, the phospholipid bilayer, transmembrane proteins (TMPs), and integral monotopic proteins (IMPs) in both the inner and outer lipid layers. We first showed that actin rings limit the longitudinal diffusion of TMPs and the IMPs of the inner leaflet but not of the IMPs of the outer leaflet. To reconcile the experimental observations, which show restricted diffusion of IMPs of the outer leaflet, with our simulations, we conjectured the existence of actin-anchored proteins that form a fence which restricts the longitudinal diffusion of IMPs of the outer leaflet. We also showed that spectrin filaments could modify transverse diffusion of TMPs and IMPs of the inner leaflet, depending on the strength of the association between lipids and spectrin. For instance, in areas where spectrin binds to the lipid bilayer, spectrin filaments would restrict diffusion of proteins within the skeleton corrals. In contrast, in areas where spectrin and lipids are not associated, spectrin modifies the diffusion of TMPs and IMPs of the inner leaflet from normal to confined-hop diffusion. Overall, we showed that diffusion of axon plasma membrane proteins is deeply anisotropic, as longitudinal diffusion is of different type than transverse diffusion. Finally, we investigated how accumulation of TMPs affects diffusion of TMPs and IMPs of both the inner and outer leaflets by changing the density of TMPs. We showed that the APMS structure acts as a fence that restricts the diffusion of TMPs and IMPs of the inner leaflet within the membrane skeleton corrals. Our findings provide insight into how the axon skeleton acts as diffusion barrier and maintains neuronal polarity.
format Online
Article
Text
id pubmed-6497228
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-64972282019-05-17 Modeling of the axon plasma membrane structure and its effects on protein diffusion Zhang, Yihao Tzingounis, Anastasios V. Lykotrafitis, George PLoS Comput Biol Research Article The axon plasma membrane consists of the membrane skeleton, which comprises ring-like actin filaments connected to each other by spectrin tetramers, and the lipid bilayer, which is tethered to the skeleton via, at least, ankyrin. Currently it is unknown whether this unique axon plasma membrane skeleton (APMS) sets the diffusion rules of lipids and proteins in the axon. To answer this question, we developed a coarse-grain molecular dynamics model for the axon that includes the APMS, the phospholipid bilayer, transmembrane proteins (TMPs), and integral monotopic proteins (IMPs) in both the inner and outer lipid layers. We first showed that actin rings limit the longitudinal diffusion of TMPs and the IMPs of the inner leaflet but not of the IMPs of the outer leaflet. To reconcile the experimental observations, which show restricted diffusion of IMPs of the outer leaflet, with our simulations, we conjectured the existence of actin-anchored proteins that form a fence which restricts the longitudinal diffusion of IMPs of the outer leaflet. We also showed that spectrin filaments could modify transverse diffusion of TMPs and IMPs of the inner leaflet, depending on the strength of the association between lipids and spectrin. For instance, in areas where spectrin binds to the lipid bilayer, spectrin filaments would restrict diffusion of proteins within the skeleton corrals. In contrast, in areas where spectrin and lipids are not associated, spectrin modifies the diffusion of TMPs and IMPs of the inner leaflet from normal to confined-hop diffusion. Overall, we showed that diffusion of axon plasma membrane proteins is deeply anisotropic, as longitudinal diffusion is of different type than transverse diffusion. Finally, we investigated how accumulation of TMPs affects diffusion of TMPs and IMPs of both the inner and outer leaflets by changing the density of TMPs. We showed that the APMS structure acts as a fence that restricts the diffusion of TMPs and IMPs of the inner leaflet within the membrane skeleton corrals. Our findings provide insight into how the axon skeleton acts as diffusion barrier and maintains neuronal polarity. Public Library of Science 2019-05-02 /pmc/articles/PMC6497228/ /pubmed/31048841 http://dx.doi.org/10.1371/journal.pcbi.1007003 Text en © 2019 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Yihao
Tzingounis, Anastasios V.
Lykotrafitis, George
Modeling of the axon plasma membrane structure and its effects on protein diffusion
title Modeling of the axon plasma membrane structure and its effects on protein diffusion
title_full Modeling of the axon plasma membrane structure and its effects on protein diffusion
title_fullStr Modeling of the axon plasma membrane structure and its effects on protein diffusion
title_full_unstemmed Modeling of the axon plasma membrane structure and its effects on protein diffusion
title_short Modeling of the axon plasma membrane structure and its effects on protein diffusion
title_sort modeling of the axon plasma membrane structure and its effects on protein diffusion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497228/
https://www.ncbi.nlm.nih.gov/pubmed/31048841
http://dx.doi.org/10.1371/journal.pcbi.1007003
work_keys_str_mv AT zhangyihao modelingoftheaxonplasmamembranestructureanditseffectsonproteindiffusion
AT tzingounisanastasiosv modelingoftheaxonplasmamembranestructureanditseffectsonproteindiffusion
AT lykotrafitisgeorge modelingoftheaxonplasmamembranestructureanditseffectsonproteindiffusion