β-III Spectrin Is Critical for Development of Purkinje Cell Dendritic Tree and Spine Morphogenesis
Open Access
- 16 November 2011
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (46), 16581-16590
- https://doi.org/10.1523/jneurosci.3332-11.2011
Abstract
Mutations in the gene encoding β-III spectrin give rise to spinocerebellar ataxia type 5, a neurodegenerative disease characterized by progressive thinning of the molecular layer, loss of Purkinje cells and increasing motor deficits. A mouse lacking full-length β-III spectrin (β-III−/−) displays a similar phenotype.In vitroandin vivoanalyses of Purkinje cells lacking β-III spectrin, reveal a critical role for β-III spectrin in Purkinje cell morphological development. Disruption of the normally well ordered dendritic arborization occurs in Purkinje cells from β-III−/−mice, specifically showing a loss of monoplanar organization, smaller average dendritic diameter and reduced densities of Purkinje cell spines and synapses. Early morphological defects appear to affect distribution of dendritic, but not axonal, proteins. This study confirms that thinning of the molecular layer associated with disease pathogenesis is a consequence of Purkinje cell dendritic degeneration, as Purkinje cells from 8-month-old β-III−/−mice have drastically reduced dendritic volumes, surface areas and total dendritic lengths compared with 5- to 6-week-old β-III−/−mice. These findings highlight a critical role of β-III spectrin in dendritic biology and are consistent with an early developmental defect in β-III−/−mice, with abnormal Purkinje cell dendritic morphology potentially underlying disease pathogenesis.Keywords
This publication has 72 references indexed in Scilit:
- -III spectrin mutation L253P associated with spinocerebellar ataxia type 5 interferes with binding to Arp1 and protein trafficking from the GolgiHuman Molecular Genetics, 2010
- Loss of β-III Spectrin Leads to Purkinje Cell Dysfunction Recapitulating the Behavior and Neuropathology of Spinocerebellar Ataxia Type 5 in HumansJournal of Neuroscience, 2010
- Spectrin mutations that cause spinocerebellar ataxia type 5 impair axonal transport and induce neurodegeneration in DrosophilaThe Journal of cell biology, 2010
- Targeted deletion of βIII spectrin impairs synaptogenesis and generates ataxic and seizure phenotypesProceedings of the National Academy of Sciences of the United States of America, 2010
- Homeostasis of intrinsic excitability in hippocampal neurones: dynamics and mechanism of the response to chronic depolarizationThe Journal of Physiology, 2010
- Axons break in animals lacking β-spectrinThe Journal of cell biology, 2007
- A postsynaptic Spectrin scaffold defines active zone size, spacing, and efficacy at the Drosophila neuromuscular junctionThe Journal of cell biology, 2006
- Presynaptic Spectrin Is Essential for Synapse StabilizationCurrent Biology, 2005
- Involvement of the glutamate receptor δ2 subunit in the long-term depression of glutamate responsiveness in cultured rat Purkinje cellsNeuroscience Letters, 1994
- Deficient Red-Cell Spectrin in Severe, Recessively Inherited SpherocytosisNew England Journal of Medicine, 1982