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Significance Neurons are highly polarized cells critical to the processing of signals within the brain, and are distinguished by morphologically and functionally distinct axonal and somatodendritic compartments. Understanding mechanisms dictating neuronal morphological specialization will advance our understanding of neuronal function and neurodegenerative diseases. This report reveals that the spectrin-actin cytoskeleton contributes to the origin of dendritic arbor morphology. We show that this cytoskeleton is required for formation and stabilization of complex dendritic arbors inDrosophila . A human spinocerebellar ataxia type 5 mutation causes β-III-spectrin to bind actin with high affinity and disrupts expansion of the spectrin-actin cytoskeleton into distal regions of the arbor. Our data suggest that loss of the spectrin-actin cytoskeleton reduces stabilization of distal dendrites required for arbor outgrowth.

β-III-spectrin spinocerebellar ataxia type 5 mutation reveals a dominant cytoskeletal mechanism that underlies dendritic arborization