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PMID:19219036

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Citation

van der Voet, M, Berends, CW, Perreault, A, Nguyen-Ngoc, T, Gönczy, P, Vidal, M, Boxem, M and van den Heuvel, S (2009) NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Galpha. Nat. Cell Biol. 11:269-77

Abstract

The spindle apparatus dictates the plane of cell cleavage, which is critical in the choice between symmetric or asymmetric division. Spindle positioning is controlled by an evolutionarily conserved pathway, which involves LIN-5/GPR-1/2/Galpha in Caenorhabditis elegans, Mud/Pins/Galpha in Drosophila and NuMA/LGN/Galpha in humans. GPR-1/2 and Galpha localize LIN-5 to the cell cortex, which engages dynein and controls the cleavage plane during early mitotic divisions in C. elegans. Here we identify ASPM-1 (abnormal spindle-like, microcephaly-associated) as a novel LIN-5 binding partner. ASPM-1, together with calmodulin (CMD-1), promotes meiotic spindle organization and the accumulation of LIN-5 at meiotic and mitotic spindle poles. Spindle rotation during maternal meiosis is independent of GPR-1/2 and Galpha, yet requires LIN-5, ASPM-1, CMD-1 and dynein. Our data support the existence of two distinct LIN-5 complexes that determine localized dynein function: LIN-5/GPR-1/2/Galpha at the cortex, and LIN-5/ASPM-1/CMD-1 at spindle poles. These functional interactions may be conserved in mammals, with implications for primary microcephaly.

Links

PubMed Online version:10.1038/ncb1834

Keywords

Animals; Caenorhabditis elegans/cytology; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/metabolism; Calmodulin/metabolism; Cell Cycle Proteins/metabolism; Cytoplasmic Dyneins; Dyneins/metabolism; Embryo, Nonmammalian/cytology; Embryo, Nonmammalian/metabolism; GTP-Binding Protein alpha Subunits/metabolism; Meiosis; Mitosis; Mitotic Spindle Apparatus/metabolism; Protein Binding; Protein Transport; Recombinant Fusion Proteins/metabolism; Rotation

Significance

Annotations

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

CAEEL:CALM

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00008107

F

Seeded From UniProt

complete

CAEEL:CALM

involved_in

GO:0032880: regulation of protein localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CALM

involved_in

GO:0051296: establishment of meiotic spindle orientation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:CALM

involved_in

GO:0051296: establishment of meiotic spindle orientation

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006840

P

Seeded From UniProt

complete

CAEEL:O17666

enables

GO:0005516: calmodulin binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00000552

F

Seeded From UniProt

complete

CAEEL:O17666

involved_in

GO:0000212: meiotic spindle organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:O17666

enables

GO:0019904: protein domain specific binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00002994

F

Seeded From UniProt

complete

CAEEL:O17666

located_in

GO:0051233: spindle midzone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:O17666

located_in

GO:0005819: spindle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:O17666

involved_in

GO:0032880: regulation of protein localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:O17666

located_in

GO:0000922: spindle pole

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:O17666

involved_in

GO:0051296: establishment of meiotic spindle orientation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:O17666

involved_in

GO:0051296: establishment of meiotic spindle orientation

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006840

P

Seeded From UniProt

complete

CAEEL:LIN5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

WB:WBGene00008107

F

Seeded From UniProt

complete

CAEEL:LIN5

located_in

GO:0051233: spindle midzone

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LIN5

located_in

GO:0005819: spindle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LIN5

involved_in

GO:0032880: regulation of protein localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:LIN5

located_in

GO:0005938: cell cortex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LIN5

located_in

GO:0000922: spindle pole

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:LIN5

involved_in

GO:0051296: establishment of meiotic spindle orientation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:LIN5

involved_in

GO:0051296: establishment of meiotic spindle orientation

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006840

P

Seeded From UniProt

complete

CAEEL:DYHC

located_in

GO:0005819: spindle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:DYHC

located_in

GO:0000922: spindle pole

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:DYHC

part_of

GO:0000922: spindle pole

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:DYHC

part_of

GO:0005819: spindle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:DYHC

involved_in

GO:0051296: establishment of meiotic spindle orientation

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00094697

P

Seeded From UniProt

complete

CAEEL:DYHC

involved_in

GO:0051296: establishment of meiotic spindle orientation

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00006840

P

Seeded From UniProt

complete


See also

References

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