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PMID:16498633

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Citation

Waragai, M, Nagamitsu, S, Xu, W, Li, YJ, Lin, X and Ashizawa, T (2006) Ataxin 10 induces neuritogenesis via interaction with G-protein beta2 subunit. J. Neurosci. Res. 83:1170-8

Abstract

Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited disorder caused by an intronic ATTCT pentanucleotide repeat expansion. The ATXN10 gene encodes a novel protein, ataxin 10, known previously as E46L, which is widely expressed in the brain. Ataxin 10 deficiency has been shown recently to cause increased apoptosis in primary cerebellar cultures, thus implicated in SCA10 pathogenesis. The biologic functions of ataxin 10 remain largely unknown. By using yeast-two-hybrid screening of a human brain cDNA library, we identified the G-protein beta2 subunit (Gbeta2) as an ataxin 10 binding partner, and the interaction was confirmed by coimmunoprecipitation and colocalization in mammalian cells in culture. Overexpression of ataxin 10 in PC12 cells induced neurite extension and enhanced neuronal differentiation induced by nerve growth factor (NGF). Moreover, coexpression of ataxin 10 and Gbeta2 potently activated the Ras-MAP kinase-Elk-1 cascade. Dominant negative Ras or inhibitor of MEK-1/2 (U0126) aborted this activation, and blocked morphologic changes, whereas inhibition of TrkA receptor by K252a had no effects. Our data suggest that the ataxin 10-Gbeta2 interaction represents a novel mechanism for inducing neuritogenesis in PC12 cells by activating the Ras-MAP kinase-Elk-1 cascade.

Links

PubMed Online version:10.1002/jnr.20807

Keywords

Animals; Brain/cytology; Brain/embryology; Brain/metabolism; COS Cells; Cell Differentiation/drug effects; Cell Differentiation/physiology; Cercopithecus aethiops; Enzyme Inhibitors/pharmacology; Extracellular Signal-Regulated MAP Kinases/metabolism; GTP-Binding Protein beta Subunits/metabolism; MAP Kinase Signaling System/drug effects; MAP Kinase Signaling System/physiology; Nerve Growth Factor/metabolism; Nerve Growth Factor/pharmacology; Nerve Tissue Proteins/metabolism; Neurites/drug effects; Neurites/metabolism; Neurites/ultrastructure; PC12 Cells; Protein Binding/physiology; Rats; Transfection; ets-Domain Protein Elk-1/metabolism; ras Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:GBB2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UBB4

F

Seeded From UniProt

complete

HUMAN:GBB2

located_in

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ATX10

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P62879

F

Seeded From UniProt

complete

HUMAN:ATX10

located_in

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ATX10

part_of

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ATX10

involved_in

GO:0031175: neuron projection development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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