NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Gα

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/Gα in Caenorhabditis elegans, Mud/Pins/ Gα in Drosophila and NuMA/LGN/Gα in humans. GPR-1/2 and Gα 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 Gα, 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/Gα 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.