A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier

Ho, Tammy Szu Yu; Zollinger, Daniel R.; Chang, Kae-Jiun; Xu, Mingxuan; Cooper, Edward C.; Stankewich, Michael C.; Bennett, Vann; Rasband, Matthew N.

doi:10.1038/nn.3859

Cited by 96 publications

(165 citation statements)

References 51 publications

Supporting

Mentioning

155

Contrasting

Order By: Relevance

“…In utero electroporation was performed as described previously (Hedstrom et al, 2007). GFP and ␣II spectrin shRNA plasmids (Galiano et al, 2012) were introduced into rat embryos at embryonic day 16 (E16). After recovery of the mother, newborn pups were killed at postnatal day 7 (P7) for immunostaining.…”

Section: Methodsmentioning

confidence: 99%

“…Spectrins comprise a submembranous cytoskeleton proposed to confer strength and flexibility to the membrane (Bennett and Baines, 2001;Xu et al, 2013). Spectrins are widely expressed and exist as tetramers consisting of two ␣ and two ␤ subunits.…”

Section: Introductionmentioning

confidence: 99%

“…␤ spectrins are not uniformly distributed throughout cells, but are often located in specialized domains. For example, ␤IV spectrin forms a complex with the scaffolding protein ankyrinG (ankG) at axon initial segments (AIS) and nodes of Ranvier to cluster the voltage-gated ion channels necessary for action potential initiation and propagation (Berghs et al, 2000;Yang et al, 2007). Due to their high degree of homology, some ␤ spectrins may compensate for one another (Ho et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…For example, ␤IV spectrin forms a complex with the scaffolding protein ankyrinG (ankG) at axon initial segments (AIS) and nodes of Ranvier to cluster the voltage-gated ion channels necessary for action potential initiation and propagation (Berghs et al, 2000;Yang et al, 2007). Due to their high degree of homology, some ␤ spectrins may compensate for one another (Ho et al, 2014). However, ␣II spectrin is the only ␣ spectrin detected in the nervous system , suggesting that, depending on its ␤ spectrin binding partner, it must play important roles in a variety of cellular contexts.…”

Section: Introductionmentioning

confidence: 99%

“…␤IV spectrin is enriched at AIS and nodes and forms a periodic lattice with actin (Xu et al, 2013;Leterrier et al, 2015;D'Este et al, 2017). ␣II spectrin is found at paranodal junctions of myelinated axons and is transiently located at developing zebrafish nodes of Ranvier (Ogawa et al, 2006;Voas et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function

Huang¹,

Zhang²,

Ho³

et al. 2017

J. Neurosci.

Self Cite

View full text Add to dashboard Cite

Spectrins form a submembranous cytoskeleton proposed to confer strength and flexibility to neurons and to participate in ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Neuronal spectrin cytoskeletons consist of diverse ␤ subunits and ␣II spectrin. Although ␣II spectrin is found in neurons in both axonal and somatodendritic domains, using proteomics, biochemistry, and superresolution microscopy, we show that ␣II and ␤IV spectrin interact and form a periodic AIS cytoskeleton. To determine the role of spectrins in the nervous system, we generated Sptan1 f/f mice for deletion of CNS ␣II spectrin. We analyzed ␣II spectrin-deficient mice of both sexes and found that loss of ␣II spectrin causes profound reductions in all ␤ spectrins. ␣II spectrin-deficient mice die before 1 month of age and have disrupted AIS and many other neurological impairments including seizures, disrupted cortical lamination, and widespread neurodegeneration. These results demonstrate the importance of the spectrin cytoskeleton both at the AIS and throughout the nervous system.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function

Huang¹,

Zhang²,

Ho³

et al. 2017

J. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

Clinical profile of autoimmune nodopathy with anti‐neurofascin 186 antibody

Liu

Zhou

Sun

et al. 2023

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective Nodal/paranodal autoantibodies identified a group of peripheral neuropathies independent from chronic inflammatory demyelinating polyneuropathy (CIDP). However, nodopathy with antibody against neurofascin 186 (NF186) was rarely reported. We presented a cohort of patients with anti‐NF186 antibody and described the clinical profile of them. Methods In this retrospective study, 195 patients diagnosed with CIDP and immune mediated idiopathic neuropathies were enrolled. Cell‐based assay was used to screen anti‐NF186 and anti‐NF155 antibodies in serum samples. Teased‐fiber immunofluorescence were used as a confirmatory assay. Clinical data of seropositive patients were collected and analyzed. Results Among the patients with anti‐NF186 antibody, seven patients (58.3%) presented acute or subacute disorder onset. Four patients (33.3%) were found to have asymmetric weakness or numbness. Distal weakness and/or numbness was the core feature. Sensory ataxia, tremor and central nervous system demyelination were rarely observed. Nerve conduction studies revealed predominant demyelinating with/without axonal loss. Brachial plexus MRI was normal in the majority of patients (6/7, 85.7%). Five patients (5/9, 55.6%) showed response to intravenous immunoglobulin. Eight patients (8/10, 80.0%) improved after corticosteroids. All patients (3/3,100%) responded to rituximab. Interpretation In the study, we depicted the clinical profile of nodopathy with anti‐NF186 antibody. The diversity of clinical features, electrophysiology results and pathological findings was specific in nodopathy with anti‐NF186 antibody. Screening of autoantibody against NF186 in acute‐onset neuropathy is recommended.

show abstract

Cargo hold and delivery: Ankyrins, spectrins, and their functional patterning of neurons

Lorenzo

2020

Cytoskeleton

View full text Add to dashboard Cite

The highly polarized, typically very long, and nonmitotic nature of neurons present them with unique challenges in the maintenance of their homeostasis. This architectural complexity serves a rich and tightly controlled set of functions that enables their fast communication with neighboring cells and endows them with exquisite plasticity. The submembrane neuronal cytoskeleton occupies a pivotal position in orchestrating the structural patterning that determines local and long‐range subcellular specialization, membrane dynamics, and a wide range of signaling events. At its center is the partnership between ankyrins and spectrins, which self‐assemble with both remarkable long‐range regularity and micro‐ and nanoscale specificity to precisely position and stabilize cell adhesion molecules, membrane transporters, ion channels, and other cytoskeletal proteins. To accomplish these generally conserved, but often functionally divergent and spatially diverse, roles these partners use a combinatorial program of a couple of dozens interacting family members, whose code is not fully unraveled. In a departure from their scaffolding roles, ankyrins and spectrins also enable the delivery of material to the plasma membrane by facilitating intracellular transport. Thus, it is unsurprising that deficits in ankyrins and spectrins underlie several neurodevelopmental, neurodegenerative, and psychiatric disorders. Here, I summarize key aspects of the biology of spectrins and ankyrins in the mammalian neuron and provide a snapshot of the latest advances in decoding their roles in the nervous system.

show abstract

A hierarchy of ankyrin-spectrin complexes clusters sodium channels at nodes of Ranvier

Cited by 96 publications

References 51 publications

αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function

αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function

Clinical profile of autoimmune nodopathy with anti‐neurofascin 186 antibody

Cargo hold and delivery: Ankyrins, spectrins, and their functional patterning of neurons

Contact Info

Product

Resources

About