Combined kinesin-1 and kinesin-3 activity drives axonal trafficking of TrkB receptors in Rab6 carriers.

Eitan Erez Zahavi, Jessica J A Hummel, Yuhao Han, Citlali Bar, Riccardo Stucchi, Maarten Altelaar, Casper C Hoogenraad

Developmental cell 2021 Feb 22

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Neurons depend on proper localization of neurotrophic receptors in their distal processes for their function. The Trk family of neurotrophin receptors controls neuronal survival, differentiation, and remodeling and are well known to function as retrograde signal carriers transported from the distal axon toward the cell body. However, the mechanism driving anterograde trafficking of Trk receptors into the axon is not well established. We used microfluidic compartmental devices and inducible secretion assay to systematically investigate the retrograde and anterograde trafficking routes of TrkB receptor along the axon in rat hippocampal neurons. We show that newly synthesized TrkB receptors traffic through the secretory pathway and are directly delivered into axon. We found that these TrkB carriers associate and are regulated by Rab6. Furthermore, the combined activity of kinesin-1 and kinesin-3 is needed for the formation of axon-bound TrkB secretory carriers and their effective entry and processive anterograde transport beyond the proximal axon. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Eitan Erez Zahavi, Jessica J A Hummel, Yuhao Han, Citlali Bar, Riccardo Stucchi, Maarten Altelaar, Casper C Hoogenraad. Combined kinesin-1 and kinesin-3 activity drives axonal trafficking of TrkB receptors in Rab6 carriers. Developmental cell. 2021 Feb 22;56(4):494-508.e7