NFASC Membrane Protein Introduction

Introduction of NFASC

Neurofascin (NFASC) is a cell adhesion molecule belonging to the L1 subgroup of the immunoglobulin superfamily, which can produce several neurofascin isoforms by alternative splicing, and their expression is temporally and spatially regulated during the development of the central and peripheral nervous systems. NFASC is localized to the Ranvier node and the axon initiation segment (AIS) of myelinated fibers, where it interacts with voltage-gated sodium channels and other proteins such as ankyrin G and β IV-spectrin. Neurofascin-155 is an oligodendrocyte product that is isolated at the membrane-like junction where the nodular ring of the myelin sheath contacts the axon surface. Neurofascin-155 interacts with the axon caspr-contact protein complex at these sites to form an electronic dense assembly of features of the nodule complex.

Function of NFASC Membrane Protein

Neurofascin-deficient mice exhibit severe ataxia, a marked decrease in motor paralysis and nerve conduction velocity, but a shortened lifespan of only 3 weeks. Deletion of neurofascin expression by adult neurons leads to slow disorganization of the axonal initial segments and pincer morphology with consequent impairment of motor learning and abolition of the spontaneous tonic discharge typical of Purkinje cells. Ablation of glial Neurofascin-155 in adult myelin glial cells results in the gradual dissolving of internodal axon joints as the neuro serine protein decreases in sphingosine levels. Some changes in the distribution of neurofascin isomers in the myelinated axon junctions are also observed in multiple sclerosis lesions. Besides, neurofascin is also a target for autoantibodies, for example, neuronal serine-specific autoantibodies are present in patients with MS, Guillain-Barré syndrome, and chronic idiopathic demyelinating neuropathy. In animal models of multiple sclerosis, these antibodies increase disease severity by disrupting axonal conduction, triggering axonal damage, and inhibiting remyelination.

Fig.1 NF155, NF186 and NF140 are isoforms of neurofascin, which share a common extracellular domain (immunoglobulin [Ig], fibronectin [FN], transmembrane [TM] and mucin) as shown. (Burnor, 2018)

Application of NFASC Membrane Protein in Literature

1. Saha R., et al. Neurofascin Knock Down in the Basolateral Amygdala Mediates Resilience of Memory and Plasticity in the Dorsal Dentate Gyrus Under Stress. Molecular Neurobiology. 2018, 55(9): 7317-7326. PubMed ID: 29404957
   
   

   This article finds that specific reduction of GABAergic inhibition in AIS synapses of BLA alters amygdala-hippocampal interactions, thereby attenuating the adverse effects of acute stress exposure on cognitive-related hippocampal function.

2. Suzuki S., et al. Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons. Scientific Reports. 2017, 7(1): 11405. PubMed ID: 28900163
   
   

   This article suggests that neurofascin alternative splicing is regulated by time and space and dynamics in cerebellar neurons.

3. Hochmeister S., et al. Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat. Plos One. 2014, 9(1): e85393. PubMed ID: 24465550
   
   

   This article suggests that placental transfer of circulating anti-neurofascin antibodies can occur and target specific structures in the CNS of developing fetuses.

4. Burnor E., et al. Neurofascin antibodies in autoimmune, genetic, and idiopathic neuropathies. Neurology. 2018, 90(1): e31-e38. PubMed ID: 29187518
   
   

   This article reveals that the frequency of neurofascin antibodies in autoimmune neuropathic samples is four times higher than that of hereditary neuropathic controls.

5. Doppler K, et al. Neurofascin-155A IgM autoantibodies in patients with inflammatory neuropathies. Journal of neurology neurosurgery and psychiatry. 2018. PubMed ID: 29945879
   
   

   This article suggests that IgM neurofascin-155 autoantibodies have test significance in patients with inflammatory neuropathy, but their pathogenic effects have yet to be verified.

NFASC Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-NFASC antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

1. Burnor E, et al. (2018). Neurofascin antibodies in autoimmune, genetic, and idiopathic neuropathies. Neurology. 90(1): e31-e38.

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