NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Galpha.
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.
van der Voet
Monique
M
Developmental Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Berends
Christian W H
CW
Perreault
Audrey
A
Nguyen-Ngoc
Tu
T
Gönczy
Pierre
P
Vidal
Marc
M
Boxem
Mike
M
van den Heuvel
Sander
S
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D056445:Cytoplasmic Dyneins; D004398:Dyneins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D008540:Meiosis; D008938:Mitosis; D011485:Protein Binding; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012399:Rotation; D008941:Spindle Apparatus / Q000378:metabolism*
C539484:Aspm-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002147:Calmodulin; D018797:Cell Cycle Proteins; D044385:GTP-Binding Protein alpha Subunits; D011993:Recombinant Fusion Proteins; C404808:lin-5 protein, C elegans; D056445:Cytoplasmic Dyneins; C502824:DHC-1 protein, C elegans; D004398:Dyneins