Annexin A2 and lamin B join membrane recycling compartments for the assembly of biomolecular condensates operating in mitotic partitioning

Abstract

Localization of the actin-, lipid- and mRNA-binding protein Annexin A2 (AnxA2) in dividing cells revealed its presence in large spherical structures which are confined to the cell periphery and frequently co-align with astral microtubules. These structures emerge at prometaphase and disappear at telophase, coinciding with the mitotic breakdown and reformation of the nuclear envelope, respectively. Their size increases towards anaphase, while their number decreases, indicating that they are capable of fusion. Treatment of cells with propylene glycol caused rapid and reversible disassembly of the structures, providing additional evidence that they correspond to biomolecular condensates. Interestingly, the condensates contain compartments operating in biosynthetic or endocytic membrane recycling - defined by Rab1, Rab11 or endocytosed transferrin - but are devoid of other membrane organelles, implying that they constitute a mitotic reservoir for selected endomembranes. They also contain lamin B, which connects with the pericentrosomal membrane recycling compartments at prometaphase, when the nuclear lamina breaks down in parallel with centrosome separation. These results suggest that the peripheral condensates correspond to the enigmatic membranous spindle matrix implicated in spindle organization and organelle inheritance. The separating daughter cells at late anaphase contain equal numbers of the condensates, in accordance with their role in mitotic partitioning of endomembranes and other cytoplasmic components.