Distinct functions of α-Spectrin and β-Spectrin during axonal pathfinding

J Hülsmeier, J Pielage, C Rickert, GM Technau… - 2007 - journals.biologists.com
J Hülsmeier, J Pielage, C Rickert, GM Technau, C Klämbt, T Stork
2007journals.biologists.com
Cell-shape changes during development require a precise coupling of the cytoskeleton with
proteins situated in the plasma membrane. Important elements controlling the shape of cells
are the Spectrin proteins that are expressed as a subcortical cytoskeletal meshwork linking
specific membrane receptors with F-actin fibers. Here, we demonstrate that Drosophila
karussell mutations affect β-spectrin and lead to distinct axonal patterning defects in the
embryonic CNS. karussell mutants display a slit-sensitive axonal phenotype characterized …
Cell-shape changes during development require a precise coupling of the cytoskeleton with proteins situated in the plasma membrane. Important elements controlling the shape of cells are the Spectrin proteins that are expressed as a subcortical cytoskeletal meshwork linking specific membrane receptors with F-actin fibers. Here, we demonstrate that Drosophila karussellmutations affect β-spectrin and lead to distinct axonal patterning defects in the embryonic CNS. karussell mutants display a slit-sensitive axonal phenotype characterized by axonal looping in stage-13 embryos. Further analyses of individual, labeled neuroblast lineages revealed abnormally structured growth cones in these animals. Cell-type-specific rescue experiments demonstrate that β-Spectrin is required autonomously and non-autonomously in cortical neurons to allow normal axonal patterning. Within the cell, β-Spectrin is associated withα-Spectrin. We show that expression of the two genes is tightly regulated by post-translational mechanisms. Loss of β-Spectrin significantly reduces levels of neuronal α-Spectrin expression, whereas gain of β-Spectrin leads to an increase in α-Spectrin protein expression. Because the loss of α-spectrin does not result in an embryonic nervous system phenotype, β-Spectrin appears to act at least partially independent of α-Spectrin to control axonal patterning.
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