PMID:17121810

Citation	Garbe, DS, Das, A, Dubreuil, RR and Bashaw, GJ (2007) beta-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila embryonic CNS. Development 134:273-84
Abstract	alpha- and beta-Spectrin are major components of a submembrane cytoskeletal network connecting actin filaments to integral plasma membrane proteins. Besides its structural role in red blood cells, the Spectrin network is thought to function in non-erythroid cells during protein targeting and membrane domain formation. Here, we demonstrate that beta-Spectrin is required in neurons for proper midline axon guidance in the Drosophila embryonic CNS. In beta-spectrin mutants many axons inappropriately cross the CNS midline, suggesting a role for beta-Spectrin in midline repulsion. Surprisingly, neither the Ankyrin-binding nor the pleckstrin homology (PH) domains of beta-Spectrin are required for accurate guidance decisions. alpha-Spectrin is dependent upon beta-Spectrin for its normal subcellular localization and/or maintenance, whereas alpha-spectrin mutants exhibit a redistribution of beta-Spectrin to the axon scaffold. beta-spectrin mutants show specific dose-dependent genetic interactions with the midline repellent slit and its neuronal receptor roundabout (robo), but not with other guidance molecules. The results suggest that beta-Spectrin contributes to midline repulsion through the regulation of Slit-Robo pathway components. We propose that the Spectrin network is playing a role independently of Ankyrin in the establishment and/or maintenance of specialized membrane domains containing guidance molecules that ensure the fidelity of axon repulsion at the midline.
Links	PubMed Online version:10.1242/dev.02653
Keywords	Animals; Animals, Genetically Modified; Ankyrins/genetics; Ankyrins/metabolism; Axons/metabolism; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/metabolism; Central Nervous System/embryology; Central Nervous System/metabolism; Drosophila/embryology; Drosophila/genetics; Drosophila/metabolism; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Female; Genes, Insect; Male; Mutation; Protein Structure, Tertiary; Spectrin/chemistry; Spectrin/genetics; Spectrin/metabolism
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