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

• DOI: 10.1523/jneurosci.2112-17.2017
• Publication Date: 2017-10-17T00:55:17Z
• Authors: Claire Yu-Mei Huang; Chuansheng Zhang; Tammy Szu-Yu Ho; Juan Oses-Prieto; Alma L. Burlingame; Joshua Lalonde; Jeffrey L. Noebels; Christophe Leterrier; Matthew N. Rasband
• Keywords: Ankyrin; EPB41

Spectrins form a submembranous cytoskeleton proposed to confer strength and flexibility neurons participate in ion channel clustering at axon initial segments (AIS) nodes of Ranvier. Neuronal spectrin cytoskeletons consist diverse β subunits αII spectrin. Although is found both axonal somatodendritic domains, using proteomics, biochemistry, superresolution microscopy, we show that βIV interact periodic AIS cytoskeleton. To determine the role spectrins nervous system, generated Sptan1 f/f mice for deletion CNS We analyzed spectrin-deficient sexes loss causes profound reductions all spectrins. die before 1 month age have disrupted many other neurological impairments including seizures, cortical lamination, widespread neurodegeneration. These results demonstrate importance throughout system. SIGNIFICANCE STATEMENT Spectrin play roles neurons, assembly excitable domains such as segment However, molecular composition structure these remain poorly understood. Here, partners with AIS. Using new conditional knock-out mouse, required assembly, neuronal excitability, protect against broad system function development important implications injuries diseases because disruption common pathology.