Ankyrin-spectrin scaffolds, from blood to brain
Date of Completion
The initiation and rapid transduction of electrical signals in the nervous system depends on the proper expression of voltage-gated sodium channels in the axon initial segment and nodes of Ranvier. The localization of sodium channel in neurons depends on two submembranous scaffolding proteins, βIV spectrin and ankyrin-G. In many cell types, ankyrins and spectrins regulate membrane protein localization and retention. However, in neurons, it is not known whether ankyrin-G or βIV spectrin is responsible for organizing the AIS and nodes of Ranvier. Here we show βIV spectrin regulates nodal membrane integrity and axon shape in a quivering mouse model. We further identify a distinct domain in βIV spectrin required for its localization to the AIS and nodes of Ranvier, and show that this domain mediates βIV spectrin's interaction with ankyrin-G. However, mutant ankyrin-G which binds to βIV spectrin fails to localize to the AIS, suggesting that binding to βIV spectrin is not sufficient for targeting ankyrin-G to the AIS. Thus, our data strongly suggest that ankyrin-G is the key intrinsic organizer for axonal membrane domain formation, while βIV spectrin is involved in the stability of these domains. ^
Yang, Yang, "Ankyrin-spectrin scaffolds, from blood to brain" (2006). Doctoral Dissertations. AAI3244589.