Adapting plasma membrane for mitotic cell rounding through Aurora A phosphorylation of numb

Cell rounding during mitosis necessitates adaptive remodeling of plasma membrane and cortical cytoskeleton. However, the underlying mechanisms remain poorly elucidated. Here, we have identified Numb phosphorylation as a pivotal mechanism in the membrane-cytoskeleton remodeling associated with mitotic cell rounding. Upon mitotic entry, Aurora A phosphorylates Numb, leading to the dissociation of Numb from plasma membrane. This is crucial for proper plasma membrane retraction, since overexpression of a non-phosphorylatable mutant or a constitutively membrane-bound variant of Numb dramatically disrupts mitotic plasma membrane retraction. Mechanistically, releasing Numb from the plasma membrane enhances the myosin I-mediated membrane-to-cortex adhesion, thereby facilitating the plasma membrane retraction accompanied with cytoskeletal withdrawal. Further analysis showed that compromised plasma membrane retraction confines mitotic cell rounding and consequently leads to spindle orientation defects. Thus, our study elucidates a phosphorylation-mediated mechanism underlying plasma membrane retraction and underscores the functional importance of this process in the context of mitotic cell rounding.