An ankyrin G–binding motif mediates TRAAK periodic localization at axon initial segments of hippocampal pyramidal neurons
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The axon initial segment (AIS) is a critical compartment in neurons. It converts post-synaptic input into action potentials that subsequently trigger information transfer to target neurons. This process relies on the presence of several voltage-gated sodium (NaV) and potassium (KV) channels that accumulate in high densities at the AIS. TRAAK is a mechanosensitive leak potassium channel that was recently localized to the nodes of Ranvier. Here, we uncover that TRAAK is also present in AISs of hippocampal and cortical neurons in the adult rat brain as well as in AISs of cultured rat hippocampal neurons. We show that the AIS localization is driven by a C-terminal ankyrin G–binding sequence that organizes TRAAK in a 190 nm spaced periodic pattern that codistributes with periodically organized ankyrin G. We furthermore uncover that while the identified ankyrin G–binding motif is analogous to known ankyrin G–binding motifs in NaV1 and KV7.2/KV7.3 channels, it was acquired by convergent evolution. Our findings identify TRAAK as an AIS ion channel that convergently acquired an ankyrin G–binding motif and expand the role of ankyrin G to include the nanoscale organization of ion channels at the AIS.
Originalsprog | Engelsk |
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Artikelnummer | e2310120121 |
Tidsskrift | Proceedings of the National Academy of Sciences of the United States of America |
Vol/bind | 121 |
Udgave nummer | 31 |
Antal sider | 11 |
ISSN | 0027-8424 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
We acknowledge the Core Facility for Integrated Microscopy (Faculty of Health and Medical Sciences, University of Copenhagen). We also want to thank Roderick MacKinnon (HHMI, The Rockefeller University, New York, NY) for providing the rabbit anti-TRAAK antibody and Martin Fredensborg Rath (Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark) for providing the rat brain sections. H.B.R. was supported by The Lundbeck Foundation (R366-2021-132).
Funding Information:
ACKNOWLEDGMENTS. We acknowledge the Core Facility for Integrated Microscopy (Faculty of Health and Medical Sciences, University of Copenhagen). We also want to thank Roderick MacKinnon (HHMI,The Rockefeller University,New York, NY) for providing the rabbit anti-TRAAK antibody and Martin Fredensborg Rath (Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark) for providing the rat brain sections. H.B.R. was supported by The Lundbeck Foundation (R366-2021-132).
Publisher Copyright:
Copyright © 2024 the Author(s).
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