Axon initial segments (AIS) and nodes of Ranvier are highly specialized axonal membrane domains enriched in Na⁺ channels. These Na⁺ channel clusters play essential roles in action potential initiation and propagation. AIS and nodal Na⁺ channel complexes are linked to the actin cytoskeleton through bIV spectrin.  However, neuronal bIV spectrin exists as two main splice variants: a longer bIVS1 variant with canonical N-terminal actin and aII spectrin-binding domains, and a shorter bIVS6 variant lacking these domains. Here, we show that the predominant neuronal bIV spectrin splice variant detected in the developing brain switches from bIVS1 tobIVS6, and that this switch is correlated with expression changes in ankyrinG splice variants. We show that bIVS1 is the predominant splice variant at nascent and developing AIS and nodes of Ranvier, but with increasing age and in adults bIVS6 becomes the main splice variant. Remarkably, super-resolution microscopy revealed that the spacing of spectrin tetramers between actin rings remains unchanged, but that shorter spectrin tetramers may also be present. Thus, during development bIV spectrin may undergo a switch in the splice variants found at AIS and nodes of Ranvier.

 

 

Collaborative Researchers

Name: Sharon R. Stevens, Matthew N. Rasband

Department: Baylor College of Medicine, USA

Institute: Department of Neuroscience

 

Name: Cristophe Leterrier

Department: Aix Marseille Université, France

Institute: Research Center for Neurobiology and Neurophysiology

 

Name: Michael C. Stankewich

Department: Yale University, USA

Institute: Department of Pathology

Funding

 

National Institutes of Health (NIH) grants NS044916 and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation