End-binding proteins EB3 and EB1 link microtubules to ankyrin G in the axon initial segment

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-05, Vol.108 (21), p.8826-8831
• Main Authors: Leterrier, Christophe, Vacher, Hélène, Fache, Marie-Pierre, d'Ortoli, Stéphanie Angles, Castets, Francis, Autillo-Touati, Amapola, Dargent, Bénédicte
• Format: Article
• Language: English
• Subjects: Animals; Ankyrins; Ankyrins - metabolism; axonal transport; Axons; Axons - metabolism; Binding sites; Biological Sciences; Cell Polarity; Cells; Comets; COS cells; Dendrites; Life Sciences; Microtubule-Associated Proteins - metabolism; Microtubules; Microtubules - metabolism; Molecular chemistry; Neurobiology; Neurons; Neurons - ultrastructure; Neurons and Cognition; Plasmids; Protein Binding; Proteins; Rats; Rats, Wistar; scaffolding proteins; Scaffolds; Up regulation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1018671108

The axon initial segment (AIS) plays a key role in maintaining the molecular and functional polarity of the neuron. The relationship between the AIS architecture and the microtubules (MTs) supporting axonal transport is unknown. Here we provide evidence that the MT plus-end-binding (EB) proteins EB1 and EB3 have a role in the AIS in addition to their MT plus-end tracking protein behavior in other neuronal compartments. In mature neurons, EB3 is concentrated and stabilized in the AIS. We identified a direct interaction between EB3/EB1 and the AIS scaffold protein ankyrin G (ankG). In addition, EB3 and EB1 participate in AIS maintenance, and AIS disassembly through ankG knockdown leads to cell-wide up-regulation of EB3 and EB1 comets. Thus, EB3 and EB1 coordinate a molecular and functional interplay between ankG and the AIS MTs that supports the central role of ankG in the maintenance of neuronal polarity.