Caytaxin deficiency disrupts signaling pathways in cerebellar cortex

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Abstract

The genetically dystonic (dt) rat, an autosomal recessive model of generalized dystonia, harbors an insertional mutation in Atcay. As a result, dt rats are deficient in Atcay transcript and the neuronally-restricted protein caytaxin. Previous electrophysiological and biochemical studies have defined olivocerebellar pathways, particularly the climbing fiber projection to Purkinje cells, as sites of significant functional abnormality in dt rats. In normal rats, Atcay transcript is abundantly expressed in the granular and Purkinje cell layers of cerebellar cortex. To better understand the consequences of caytaxin deficiency in cerebellar cortex, differential gene expression was examined in dt rats and their normal littermates. Data from oligonucleotide microarrays and quantitative real-time reverse transcriptase-PCR (QRT-PCR) identified phosphatidylinositol signaling pathways, calcium homeostasis, and extracellular matrix interactions as domains of cellular dysfunction in dt rats. In dt rats, genes encoding the corticotropin-releasing hormone receptor 1 (CRH-R1, Crhr1) and plasma membrane calcium-dependent ATPase 4 (PMCA4, Atp2b4) showed the greatest up-regulation with QRT-PCR. Immunocytochemical experiments demonstrated that CRH-R1, CRH, and PMCA4 were up-regulated in cerebellar cortex of mutant rats. Along with previous electrophysiological and pharmacological studies, our data indicate that caytaxin plays a critical role in the molecular response of Purkinje cells to climbing fiber input. Caytaxin may also contribute to maturational events in cerebellar cortex.

Original languageEnglish (US)
Pages (from-to)439-461
Number of pages23
JournalNeuroscience
Volume144
Issue number2
DOIs
StatePublished - Jan 19 2007

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Cerebellar Cortex
Purkinje Cells
Reverse Transcriptase Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Plasma Membrane Calcium-Transporting ATPases
Corticotropin-Releasing Hormone Receptors
Calcium Signaling
Dystonia
Phosphatidylinositols
Oligonucleotide Array Sequence Analysis
Extracellular Matrix
Homeostasis
Up-Regulation
Pharmacology
Gene Expression
Mutation

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Caytaxin deficiency disrupts signaling pathways in cerebellar cortex. / Xiao, Jianfeng; Gong, S.; Ledoux, Mark.

In: Neuroscience, Vol. 144, No. 2, 19.01.2007, p. 439-461.

Research output: Contribution to journalArticle

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