Developmental mechanism of the periodic membrane skeleton in axons

Zhong, Guisheng; He, Jiang; Zhou, Ruobo; Lorenzo, Damaris N.; Babcock, Hazen P.; Bennett, Vann; Zhuang, Xiaowei

doi:10.7554/elife.04581

Cited by 211 publications

(495 citation statements)

References 58 publications

(107 reference statements)

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“…The 'axonal skeleton' helps axons to maintain their mechanical stability and conduct impulses. This understanding is supported by other studies 5 , which show that worms genetically engineered to lack the protein that connect the rings have fragile axons, impaired movement and a reduced response to mechanical stimuli.…”

Section: Cells In Focussupporting

confidence: 73%

Cell imaging: Beyond the limits

Bourzac¹

2015

Nature

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Section: Cells In Focussupporting

confidence: 73%

Cell imaging: Beyond the limits

Bourzac¹

2015

Nature

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“…Stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion (STED) microscopy were indeed crucial for the identification of a ∼190-nm periodic organization of the key components of the AIS. In particular, a periodic spatial arrangement was discovered for cytoskeletal proteins (actin, ankyrin G, betaIV spectrin), adhesion molecules (neurofascin), and channels (voltage-gated sodium Na v channels) (1)(2)(3)(4). In the distal part of the axon, this periodicity has been found for actin, adducin, ankyrin B, and betaII spectrin in virtually every neuron type from the central and peripheral nervous systems (CNS and PNS) (1,2,5,6).…”

mentioning

confidence: 97%

Ultrastructural anatomy of nodes of Ranvier in the peripheral nervous system as revealed by STED microscopy

D’Este

Kamin

Balzarotti

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

116

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We used stimulated emission depletion (STED) superresolution microscopy to analyze the nanoscale organization of 12 glial and axonal proteins at the nodes of Ranvier of teased sciatic nerve fibers. Cytoskeletal proteins of the axon (betaIV spectrin, ankyrin G) exhibit a high degree of one-dimensional longitudinal order at nodal gaps. In contrast, axonal and glial nodal adhesion molecules [neurofascin-186, neuron glial-related cell adhesion molecule (NrCAM)] can arrange in a more complex, 2D hexagonal-like lattice but still feature a ∼190-nm periodicity. Such a lattice-like organization is also found for glial actin. Sodium and potassium channels exhibit a one-dimensional periodicity, with the Na v channels appearing to have a lower degree of organization. At paranodes, both axonal proteins (betaII spectrin, Caspr) and glial proteins (neurofascin-155, ankyrin B) form periodic quasi-one-dimensional arrangements, with a high degree of interdependence between the position of the axonal and the glial proteins. The results indicate the presence of mechanisms that finely align the cytoskeleton of the axon with the one of the Schwann cells, both at paranodal junctions (with myelin loops) and at nodal gaps (with microvilli). Taken together, our observations reveal the importance of the lateral organization of proteins at the nodes of Ranvier and pave the way for deeper investigations of the molecular ultrastructural mechanisms involved in action potential propagation, the formation of the nodes, axon-glia interactions, and demyelination diseases.nodes of Ranvier | STED nanoscopy | cytoskeleton | axon-glia interaction | sciatic nerve I n recent years, knowledge of the ultrastructural organization of the axon initial segment (AIS) has been greatly extended by using optical nanoscopy to visualize its molecular composition. Stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion (STED) microscopy were indeed crucial for the identification of a ∼190-nm periodic organization of the key components of the AIS. In particular, a periodic spatial arrangement was discovered for cytoskeletal proteins (actin, ankyrin G, betaIV spectrin), adhesion molecules (neurofascin), and channels (voltage-gated sodium Na v channels) (1-4). In the distal part of the axon, this periodicity has been found for actin, adducin, ankyrin B, and betaII spectrin in virtually every neuron type from the central and peripheral nervous systems (CNS and PNS) (1, 2, 5, 6). Although myelination of axons does not alter the patterning of the subcortical cytoskeleton (5, 6), it changes its molecular composition, promoting the clustering of specific markers at the nodes of Ranvier, where the action potential is regenerated (reviewed in refs. 7, 8). At nodes of Ranvier, the myelin sheath formed by oligodendrocytes (in the CNS) or Schwann cells (in the PNS) is interrupted. Still, the nodal gap is surrounded by perinodal astrocytes and microvilli stemming from the Schwann cells in the CNS and PNS, respectively (9). Interestingly, the AIS an...

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“…S4A). This may indicate a variation in the local concentration of spectrin βV, because it has previously been shown in neurons that the local concentration of β spectrin (βII in that case) is critical for its organization into a periodic skeleton (22). In the mouse vestibular hair cells (type I and type II), spectrin βV was detected as dispersed cytoplasmic immunoreactive puncta spreading from the cell apical region near the cuticular plate down to the juxtanuclear region (Figs.…”

Section: Differential Distribution Of Spectrin βV In Amphibian and Mamentioning

confidence: 97%

“…S6). Likewise, the spreading of an actin-and spectrinbased cortical lattice has been reported in developing neuronal cells: the cortical skeleton of axons, a periodic structure formed by actin rings connected by flexible filaments made of βII, βIII, or βIV spectrin, is initiated next to the cell body and gradually extends to the axon terminals (22,33,34).…”

Section: And Ref 30)mentioning

confidence: 99%

Spectrin βV adaptive mutations and changes in subcellular location correlate with emergence of hair cell electromotility in mammalians

Cortese

Papal

Pisciottano

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The remarkable hearing capacities of mammals arise from various evolutionary innovations. These include the cochlear outer hair cells and their singular feature, somatic electromotility, i.e., the ability of their cylindrical cell body to shorten and elongate upon cell depolarization and hyperpolarization, respectively. To shed light on the processes underlying the emergence of electromotility, we focused on the βV giant spectrin, a major component of the outer hair cells' cortical cytoskeleton. We identified strong signatures of adaptive evolution at multiple sites along the spectrin-βV amino acid sequence in the lineage leading to mammals, together with substantial differences in the subcellular location of this protein between the frog and the mouse inner ear hair cells. In frog hair cells, spectrin βV was invariably detected near the apical junctional complex and above the cuticular plate, a dense F-actin meshwork located underneath the apical plasma membrane. In the mouse, the protein had a broad punctate cytoplasmic distribution in the vestibular hair cells, whereas it was detected in the entire lateral wall of cochlear outer hair cells and had an intermediary distribution (both cytoplasmic and cortical, but restricted to the cell apical region) in cochlear inner hair cells. Our results support a scenario where the singular organization of the outer hair cells' cortical cytoskeleton may have emerged from molecular networks initially involved in membrane trafficking, which were present near the apical junctional complex in the hair cells of mammalian ancestors and would have subsequently expanded to the entire lateral wall in outer hair cells.unconventional spectrins | inner ear | F-actin cytoskeleton | cortical lattice | phylogenetics T he response of the mammalian auditory organ (cochlea) to acoustic stimuli in an extended frequency range (including high frequencies) has remarkable properties including very high sensitivity and exquisitely sharp tuning (1-3). These properties are the consequence of an evolutionary process that involved major morphological and functional changes. One of them is the emergence, in the cochlea, of the outer hair cells, a unique type of specialized sensory cells that display somatic electromotility, i.e., they undergo periodic length changes in response to the oscillation of their membrane potential evoked by the sound wave (they shorten upon depolarization and elongate upon hyperpolarization) (SI Appendix, Fig. S1 A-C). This process has endowed the mammalian auditory organ with a singular mechanism of spectral analysis of the acoustic stimulus through frequencyselective mechanical amplification (1-3), whereas spectral analysis in other vertebrates (fish, amphibians, reptiles, and birds) primarily relies on electrical tuning of the hair cells (4, 5).An intriguing question is how the emergence of somatic electromotility is related with the evolution of individual proteins involved in this process. The electromotility of outer hair cells critically depends on the presence, in th...

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Developmental mechanism of the periodic membrane skeleton in axons

Cited by 211 publications

References 58 publications

Cell imaging: Beyond the limits

Cell imaging: Beyond the limits

Ultrastructural anatomy of nodes of Ranvier in the peripheral nervous system as revealed by STED microscopy

Spectrin βV adaptive mutations and changes in subcellular location correlate with emergence of hair cell electromotility in mammalians

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