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Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment.

Publication ,  Journal Article
Ango, F; di Cristo, G; Higashiyama, H; Bennett, V; Wu, P; Huang, ZJ
Published in: Cell
October 15, 2004

Distinct classes of GABAergic synapses are segregated into subcellular domains (i.e., dendrite, soma, and axon initial segment-AIS), thereby differentially regulating the input, integration, and output of principal neurons. In cerebellum, for example, basket interneurons make exquisitely precise "pinceau synapses" on AIS of Purkinje neurons, but the underlying mechanism is unknown. Using BAC transgenic reporter mice, we found that basket axons always contacted Purkinje soma before innervating AIS. This synapse targeting process followed the establishment of a subcellular gradient of neurofascin186 (NF186), an L1 family immunoglobulin cell adhesion molecule (L1CAM), along the Purkinje AIS-soma axis. This gradient was dependent on ankyrinG, an AIS-restricted membrane adaptor protein that recruits NF186. In the absence of neurofascin gradient, basket axons lost directional growth along Purkinje neurons and precisely followed NF186 to ectopic locations. Disruption of NF186-ankyrinG interactions at AIS reduced pinceau synapse formation. These results implicate ankyrin-based localization of L1CAMs in subcellular organization of GABAergic synapses.

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

October 15, 2004

Volume

119

Issue

2

Start / End Page

257 / 272

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synapses
  • Purkinje Cells
  • Nerve Growth Factors
  • Models, Neurological
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Immunoglobulins
  • Developmental Biology
 

Citation

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Ango, F., di Cristo, G., Higashiyama, H., Bennett, V., Wu, P., & Huang, Z. J. (2004). Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment. Cell, 119(2), 257–272. https://doi.org/10.1016/j.cell.2004.10.004
Ango, Fabrice, Graziella di Cristo, Hiroyuki Higashiyama, Vann Bennett, Priscilla Wu, and Z Josh Huang. “Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment.Cell 119, no. 2 (October 15, 2004): 257–72. https://doi.org/10.1016/j.cell.2004.10.004.
Ango, Fabrice, et al. “Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment.Cell, vol. 119, no. 2, Oct. 2004, pp. 257–72. Pubmed, doi:10.1016/j.cell.2004.10.004.
Ango F, di Cristo G, Higashiyama H, Bennett V, Wu P, Huang ZJ. Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment. Cell. 2004 Oct 15;119(2):257–272.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

October 15, 2004

Volume

119

Issue

2

Start / End Page

257 / 272

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synapses
  • Purkinje Cells
  • Nerve Growth Factors
  • Models, Neurological
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Immunoglobulins
  • Developmental Biology