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PMID:21562226

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Citation

Wang, Y, Steimle, PA, Ren, Y, Ross, CA, Robinson, DN, Egelhoff, TT, Sesaki, H and Iijima, M (2011) Dictyostelium huntingtin controls chemotaxis and cytokinesis through the regulation of myosin II phosphorylation. Mol. Biol. Cell 22:2270-81

Abstract

Abnormalities in the huntingtin protein (Htt) are associated with Huntington's disease. Despite its importance, the function of Htt is largely unknown. We show that Htt is required for normal chemotaxis and cytokinesis in Dictyostelium discoideum. Cells lacking Htt showed slower migration toward the chemoattractant cAMP and contained lower levels of cortical myosin II, which is likely due to defects in dephosphorylation of myosin II mediated by protein phosphatase 2A (PP2A). htt(-) cells also failed to maintain myosin II in the cortex of the cleavage furrow, generating unseparated daughter cells connected through a thin cytoplasmic bridge. Furthermore, similar to Dictyostelium htt(-) cells, siRNA-mediated knockdown of human HTT also decreased the PP2A activity in HeLa cells. Our data indicate that Htt regulates the phosphorylation status of myosin II during chemotaxis and cytokinesis through PP2A.

Links

PubMed PMC3128529 Online version:10.1091/mbc.E10-11-0926

Keywords

Cell Division/genetics; Cell Division/radiation effects; Cell Movement/genetics; Cell Movement/physiology; Cells, Cultured; Chemotaxis/genetics; Chemotaxis/physiology; Cyclic AMP/metabolism; Cytokinesis/physiology; Dictyostelium/cytology; Dictyostelium/genetics; Dictyostelium/metabolism; HeLa Cells; Humans; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Myosin Type II/genetics; Myosin Type II/metabolism; Phosphorylation; Protein Phosphatase 2/metabolism; Protozoan Proteins/genetics; Protozoan Proteins/metabolism

Significance

Annotations

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

DICDI:PH2AB

enables

GO:0019888: protein phosphatase regulator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DICDI:2AAA

enables

GO:0005198: structural molecule activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DICDI:HD

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DICDI:PP2AA

enables

GO:0004722: protein serine/threonine phosphatase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HD

acts_upstream_of_or_within

GO:0043666: regulation of phosphoprotein phosphatase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:HD

acts_upstream_of_or_within

GO:0043666: regulation of phosphoprotein phosphatase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:HD

acts_upstream_of_or_within

GO:0043327: chemotaxis to cAMP

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:HD

acts_upstream_of_or_within

GO:0043520: regulation of myosin II filament assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:HD

acts_upstream_of_or_within

GO:0060176: regulation of aggregation involved in sorocarp development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:HD

acts_upstream_of_or_within

GO:0061952: midbody abscission

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DICDI:HD

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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