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

Jörn Hülsmeier, Jan Pielage, Christof Rickert, Gerd M. Technau, Christian Klämbt, Tobias Stork

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

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 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 with α-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.

Original languageEnglish (US)
Pages (from-to)713-722
Number of pages10
JournalDevelopment
Volume134
Issue number4
DOIs
StatePublished - Feb 2007
Externally publishedYes

Keywords

  • Drosophila
  • Growth cone
  • Nervous system
  • Spectrin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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