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

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). pp. 257-72. ISSN 0092-8674 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/15479642
DOI: 10.1016/j.cell.2004.10.004

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Animals Ankyrins metabolism Axons metabolism Cell Adhesion Molecules metabolism Cell Polarity Cell Shape Chemotaxis physiology Immunoglobulins metabolism Mice Mice Inbred C57BL Mice Transgenic Models, Neurological Nerve Growth Factors metabolism Purkinje Cells cytology metabolism Synapseschemistry physiology gamma-Aminobutyric Acid metabolism
Subjects: bioinformatics > genomics and proteomics > small molecules > GABAergic
organs, tissues, organelles, cell types and functions > tissues types and functions > axon
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Huang lab
Depositing User: CSHL Librarian
Date Deposited: 05 Apr 2012 15:34
Last Modified: 10 May 2013 18:55
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25786

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