beta-Spectrin functions independently of Ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila embryonic CNS.
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.
Garbe
David S
DS
Department of Neuroscience, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Das
Amlan
A
Dubreuil
Ronald R
RR
Bashaw
Greg J
GJ
D000818:Animals; D030801:Animals, Genetically Modified; D017487:Ankyrins / Q000235:genetics / Q000378:metabolism*; D001369:Axons / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology* / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D008297:Male; D009154:Mutation; D017434:Protein Structure, Tertiary; D013049:Spectrin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D017487:Ankyrins; D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; D013049:Spectrin