ArticleProceedings of the National Academy of Sciences of the United States of America2020
Mechanistic insights into the interactions of dynein regulator Ndel1 with neuronal ankyrins and implications in polarity maintenance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 22 citations in OpenAlex.
- A functional role for Septin-2 in the maintenance of the axon initial segment and in human cognitive development.Brain : a journal of neurology · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Ankyrin-G and Its Binding Partners in Neurons: Orchestrating the Molecular Structure of the Axon Initial Segment.Biomolecules · 2025Review
- CCSer2 gates dynein activity at the cell periphery.The Journal of cell biology · 2025Article
- Sculpting excitable membranes: voltage-gated ion channel delivery and distribution.Nature reviews. Neuroscience · 2025Review
- Roles of ANK2/ankyrin-B in neurodevelopmental disorders: Isoform functions and implications for autism spectrum disorder and epilepsy.Current opinion in neurobiology · 2025Review
- CCSer2 gates dynein activity at the cell periphery.bioRxiv : the preprint server for biology · 2024Article
- Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.Molecular psychiatry · 2023Article
- Impaired disassembly of the axon initial segment restricts mitochondrial entry into damaged axons.The EMBO journal · 2022Article
- Mechanisms underlying the role of ankyrin-B in cardiac and neurological health and disease.Frontiers in cardiovascular medicine · 2022Review
- Nde1 and Ndel1: Outstanding Mysteries in Dynein-Mediated Transport.Frontiers in cell and developmental biology · 2022Review
- Roles of palmitoylation in structural long-term synaptic plasticity.Molecular brain · 2021Review
- Cytoskeletal organization of axons in vertebrates and invertebrates.The Journal of cell biology · 2020Article
- Cargo hold and delivery: Ankyrins, spectrins, and their functional patterning of neurons.Cytoskeleton (Hoboken, N.J.) · 2020Review
- Postnatal Role of the Cytoskeleton in Adult Epileptogenesis.Cerebral cortex communications · 2020Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ankyrin-G (AnkG), a highly enriched scaffold protein in the axon initial segment (AIS) of neurons, functions to maintain axonal polarity and the integrity of the AIS. At the AIS, AnkG regulates selective intracellular cargo trafficking between soma and axons via interaction with the dynein regulator protein Ndel1, but the molecular mechanism underlying this binding remains elusive. Here we report that Ndel1's C-terminal coiled-coil region (CT-CC) binds to giant neuron-specific insertion regions present in both AnkG and AnkB with 2:1 stoichiometry. The high-resolution crystal structure of AnkB in complex with Ndel1 CT-CC revealed the detailed molecular basis governing the AnkB/Ndel1 complex formation. Mechanistically, AnkB binds with Ndel1 by forming a stable 5-helix bundle dominated by hydrophobic interactions spread across 6 distinct interaction layers. Moreover, we found that AnkG is essential for Ndel1 accumulation at the AIS. Finally, we found that cargo sorting at the AIS can be disrupted by blocking the AnkG/Ndel1 complex formation using a peptide designed based on our structural data. Collectively, the atomic structure of the AnkB/Ndel1 complex together with studies of cargo sorting through the AIS establish the mechanistic basis for AnkG/Ndel1 complex formation and for the maintenance of axonal polarity. Our study will also be valuable for future studies of the interaction between AnkB and Ndel1 perhaps at distal axonal cargo transport.
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