Disruption of the MAP1B-related protein FUTSCH leads to changes in the neuronal cytoskeleton, axonal transport defects, and progressive neurodegeneration in Drosophila

Alexandre Bettencourt Da Cruz, Martin Schwärzel, Sabine Schulze, Mahtab Niyyati, Martin Heisenberg, Doris Kretzschmar

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The elaboration of neuronal axons and dendrites is dependent on a functional cytoskeleton. Cytoskeletal components have been shown to play a major role in the maintenance of the nervous system through adulthood, and changes in neurofilaments and microtubule-associated proteins (MAPs) have been linked to a variety of neurodegenerative diseases. Here we show that Futsch, the fly homolog of MAP1B, is involved in progressive neurodegeneration. Although Futsch is widely expressed throughout the CNS, degeneration in futscholk primarily occurs in the olfactory system and mushroom bodies. Consistent with the predicted function of Futsch, we find abnormalities in the microtubule network and defects in axonal transport. Degeneration in the adult brain is preceded by learning deficits, revealing a neuronal dysfunction before detectable levels of cell death. Futsch is negatively regulated by the Drosophila Fragile X mental retardation gene, and a mutation in this gene delays the onset of neurodegeneration in futscholk. A similar effect is obtained by expression of either fly or bovine tau, suggesting a certain degree of functional redundancy of MAPs. The futscholk mutants exhibit several characteristics of human neurodegenerative diseases, providing an opportunity to study the role of MAPs in progressive neurodegeneration within an experimentally accessible, in vivo model system.

Original languageEnglish (US)
Pages (from-to)2433-2442
Number of pages10
JournalMolecular Biology of the Cell
Volume16
Issue number5
DOIs
StatePublished - May 2005

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Axonal Transport
Microtubule-Associated Proteins
Cytoskeleton
Drosophila
Diptera
Neurodegenerative Diseases
Mushroom Bodies
Proteins
Intermediate Filaments
Dendrites
Microtubules
Intellectual Disability
Nervous System
Genes
Axons
Cell Death
Maintenance
Learning
Mutation
Brain

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Disruption of the MAP1B-related protein FUTSCH leads to changes in the neuronal cytoskeleton, axonal transport defects, and progressive neurodegeneration in Drosophila. / Da Cruz, Alexandre Bettencourt; Schwärzel, Martin; Schulze, Sabine; Niyyati, Mahtab; Heisenberg, Martin; Kretzschmar, Doris.

In: Molecular Biology of the Cell, Vol. 16, No. 5, 05.2005, p. 2433-2442.

Research output: Contribution to journalArticle

Da Cruz, Alexandre Bettencourt ; Schwärzel, Martin ; Schulze, Sabine ; Niyyati, Mahtab ; Heisenberg, Martin ; Kretzschmar, Doris. / Disruption of the MAP1B-related protein FUTSCH leads to changes in the neuronal cytoskeleton, axonal transport defects, and progressive neurodegeneration in Drosophila. In: Molecular Biology of the Cell. 2005 ; Vol. 16, No. 5. pp. 2433-2442.
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