title: Nanoscopic compartmentalization of membrane protein motion at the axon initial segment.
abstract: The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. Here, we performed single-particle tracking time-course experiments on hippocampal neurons during AIS development. We analyzed the mobility of lipid-anchored molecules by high-speed single-particle tracking and correlated positions of membrane molecules with the nanoscopic organization of the AIS cytoskeleton. We observe a strong reduction in mobility early in AIS development. Membrane protein motion in the AIS plasma membrane is confined to a repetitive pattern of ∼190-nm-spaced segments along the AIS axis as early as day in vitro 4, and this pattern alternates with actin rings. Mathematical modeling shows that diffusion barriers between the segments significantly reduce lateral diffusion along the axon.
authors.affiliation: Institute for Chemistry and Biochemistry, Free University Berlin, 14195 Berlin, Germany Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK Institute for Biochemistry, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: David
authors.identifier: http://orcid.org/0000-0001-9455-1134
authors.initials: D
authors.lastname: Albrecht
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK Institute for Biochemistry, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Christian M
authors.identifier: http://orcid.org/0000-0001-5621-3695
authors.initials: CM
authors.lastname: Winterflood
authors.affiliation: Department of Mathematics and Computer Science, Free University Berlin, 14195 Berlin, Germany.
authors.forename: Mohsen
authors.identifier: http://orcid.org/0000-0002-7698-5630
authors.initials: M
authors.lastname: Sadeghi
authors.affiliation: Institute for Biochemistry, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0003-3323-034X
authors.initials: T
authors.lastname: Tschager
authors.affiliation: Department of Mathematics and Computer Science, Free University Berlin, 14195 Berlin, Germany.
authors.forename: Frank
authors.identifier: http://orcid.org/0000-0003-4169-9324
authors.initials: F
authors.lastname: Noé
authors.affiliation: Institute for Chemistry and Biochemistry, Free University Berlin, 14195 Berlin, Germany Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK Institute for Biochemistry, ETH Zurich, 8093 Zurich, Switzerland helge.ewers@fu-berlin.de.
authors.forename: Helge
authors.identifier: http://orcid.org/0000-0003-3948-4332
authors.initials: H
authors.lastname: Ewers
mesh_terms: D000818:Animals; D000071040:Axon Initial Segment / Q000378:metabolism*; D002451:Cell Compartmentation; D058948:Cell Tracking; D002478:Cells, Cultured; D004058:Diffusion; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D045663:Quantum Dots / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013049:Spectrin / Q000378:metabolism
chemical_list: D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D013049:Spectrin; D049452:Green Fluorescent Proteins