Developmental mechanism of the periodic membrane skeleton in axons.
Date
2014-12-23
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Attention Stats
Abstract
Actin, spectrin, and associated molecules form a periodic sub-membrane lattice structure in axons. How this membrane skeleton is developed and why it preferentially forms in axons are unknown. Here, we studied the developmental mechanism of this lattice structure. We found that this structure emerged early during axon development and propagated from proximal regions to distal ends of axons. Components of the axon initial segment were recruited to the lattice late during development. Formation of the lattice was regulated by the local concentration of βII spectrin, which is higher in axons than in dendrites. Increasing the dendritic concentration of βII spectrin by overexpression or by knocking out ankyrin B induced the formation of the periodic structure in dendrites, demonstrating that the spectrin concentration is a key determinant in the preferential development of this structure in axons and that ankyrin B is critical for the polarized distribution of βII spectrin in neurites.
Type
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Zhong, Guisheng, Jiang He, Ruobo Zhou, Damaris Lorenzo, Hazen P Babcock, Vann Bennett and Xiaowei Zhuang (2014). Developmental mechanism of the periodic membrane skeleton in axons. Elife, 3. 10.7554/eLife.04581 Retrieved from https://hdl.handle.net/10161/10975.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke
Vann Bennett
Functional organization of vertebrate plasma membranes: Molecules to Physiology
Our laboratory discovered ankyrins and their function in coordinating functionally related membrane-spanning proteins within micron-scale compartments in vertebrate plasma membranes. Ankyrin-dependent compartments include excitable membranes responsible for initiation and propagation of action potentials in the nervous system, and for rhythmic beating of the heart. Cytoplasmic domains of membrane transporters and cell adhesion proteins (15 protein families identified so far) associate on the inner surface of the plasma membrane with members of the ankyrin family. Ankyrins recognize intrinsically disordered regions within these cytoplasmic domains through independently evolved interactions with a highly conserved extended peptide-binding groove formed by the ANK repeat solenoid. The ANK repeat solenoid accommodates multiple membrane-spanning partners and can cluster these proteins within nanodomains. Ankyrins and their partners are in turn coupled to spectrins, which are elongated organelle-sized proteins that form mechanically resilient networks on the cytoplasmic surfaces of plasma membrane domains. Spectins are cross-linked by actin protofilaments capped on their fast-growing ends by adducin. In addition, giant vertebrate ankyrins with specialized roles in neurons acquired new coding sequences by exon shuffling early in vertebrate evolution. Giant ankyrin-G co-evolved with the axon initial segment and myelination, and functions as a master organizer of this domain through recruitment of voltage-gated sodium channels, KCNQ2/3 channels, L1Cam family cell adhesion molecules, beta-4 spectrin, and microtubules. Mutations of ankyrins and spectrins result in human disease including hereditary anemia, cardiac arrhythmia, autism and neurodevelopmental disorders.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.