RGD Reference Report - Cooperative Interactions between 480 kDa Ankyrin-G and EB Proteins Assemble the Axon Initial Segment. - Rat Genome Database

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Cooperative Interactions between 480 kDa Ankyrin-G and EB Proteins Assemble the Axon Initial Segment.

Authors: Freal, A  Fassier, C  Le Bras, B  Bullier, E  De Gois, S  Hazan, J  Hoogenraad, CC  Couraud, F 
Citation: Freal A, etal., J Neurosci. 2016 Apr 20;36(16):4421-33. doi: 10.1523/JNEUROSCI.3219-15.2016.
RGD ID: 11535813
Pubmed: PMID:27098687   (View Abstract at PubMed)
PMCID: PMC6601828   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3219-15.2016   (Journal Full-text)

The axon initial segment (AIS) is required for generating action potentials and maintaining neuronal polarity. Significant progress has been made in deciphering the basic building blocks composing the AIS, but the underlying mechanisms required for AIS formation remains unclear. The scaffolding protein ankyrin-G is the master-organizer of the AIS. Microtubules and their interactors, particularly end-binding proteins (EBs), have emerged as potential key players in AIS formation. Here, we show that the longest isoform of ankyrin-G (480AnkG) selectively associates with EBs via its specific tail domain and that this interaction is crucial for AIS formation and neuronal polarity in cultured rodent hippocampal neurons. EBs are essential for 480AnkG localization and stabilization at the AIS, whereas 480AnkG is required for the specific accumulation of EBs in the proximal axon. Our findings thus provide a conceptual framework for understanding how the cooperative relationship between 480AnkG and EBs induces the assembly of microtubule-AIS structures in the proximal axon. SIGNIFICANCE STATEMENT: Neuronal polarity is crucial for the proper function of neurons. The assembly of the axon initial segment (AIS), which is the hallmark of early neuronal polarization, relies on the longest 480 kDa ankyrin-G isoform. The microtubule cytoskeleton and its interacting proteins were suggested to be early key players in the process of AIS formation. In this study, we show that the crosstalk between 480 kDa ankyrin-G and the microtubule plus-end tracking proteins, EBs, at the proximal axon is decisive for AIS assembly and neuronal polarity. Our work thus provides insight into the functional mechanisms used by 480 kDa ankyrin-G to drive the AIS formation and thereby to establish neuronal polarity.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ank3Rataxon development  IMP  RGD 
Ank3Ratestablishment or maintenance of microtubule cytoskeleton polarity  IMP  RGD 
Ank3Ratmaintenance of protein location in cell  IMP  RGD 
Ank3Ratprotein localization to axon  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ank3  (ankyrin 3)


Additional Information