p27Kip1 Is a Microtubule-Associated Protein that Promotes Microtubule Polymerization during Neuron Migration

SummaryThe migration of cortical interneurons is characterized by extensive morphological changes that result from successive cycles of nucleokinesis and neurite branching. Their molecular bases remain elusive, and the present work describes how p27Kip1 controls cell-cycle-unrelated signaling pathways to regulate these morphological remodelings. Live imaging reveals that interneurons lacking p27Kip1 show delayed tangential migration resulting from defects in both nucleokinesis and dynamic branching of the leading process. At the molecular level, p27Kip1 is a microtubule-associated protein that promotes polymerization of microtubules in extending neurites, thereby contributing to tangential migration. Furthermore, we show that p27Kip1 controls actomyosin contractions that drive both forward translocation of the nucleus and growth cone splitting. Thus, p27Kip1 cell-autonomously controls nucleokinesis and neurite branching by regulating both actin and microtubule cytoskeletons.

► p27 regulates interneuron migration by remodeling both actin and microtubules (MT)
► p27 is MT associated and promotes MT polymerization to support neurite outgrowth
► MT control is separable from effects on RhoA GTPase and actomyosin contractility
► p27 controls actomyosin contractility for nucleokinesis and neurite branch splitting