Assembly of the Axon Initial Segment (AIS): role of a distal axonal cytoskeleton

MAURICIO R. GALIANO

Huerta Grande, Cordoba

Congreso; XXVIII Congreso de la Sociedad Argentina de Investigación en Neurociencias & Reunión Satélite: ?Bases Neurales de la Conducta: Neuroetología y Neurobiología de la Memoria en el Cono Sur?; 2013

XXVIII Congreso de la Sociedad Argentina de Investigación en Neurociencias

The AIS is a specialized domain located at the initial portion of the axon with essential roles on action potential firing and maintenance of neuronal polarity. The formation and maintenance of the AIS mainly depends on the enrichment of the membrane adaptor protein Ankyrin-G (AnkG), which clusters ion channels at this domain and organizes a specialized cytoskeleton beneath the AIS. This study focused on how ankG is recruited to the AIS. By immunohistochemical analysis was observed that after axonal specification, AnkG is clustered at the same axonal location proximal to the cell body, during development. In this sense, it was defined a distinct submembranous cytoskeleton comprised of Ankyrin-B, αIIspectrin and βII-spectrin, that is formed from the distal axon generating an intraaxonal boundary that restricts AnkG to AIS. The overexpression of these individual components of distal cytoskeleton modified the location of this boundary altering the AIS length. As well, after knockdown of Ankyrin-B, αII-spectrin or βII-spectrin, a strong impairment of AnkG clustering at the AIS was observed. Moreover, disrupted AIS were also observed in αII-spectrin and βII-spectrin deficient mice supporting these findings. Thus, AnkG clustering at the AIS takes place by an exclusion mechanism driven by the distal axonal cytoskeleton.