Radial intercalation is regulated by the Par complex and the microtubule-stabilizing protein CLAMP/Spef1
JOURNAL OF CELL BIOLOGY
Authors: Werner, Michael E.; Mitchell, Jennifer W.; Putzbach, William; Bacon, Elizabeth; Kim, Sun K.; Mitchell, Brian J.
Abstract
The directed movement of cells is critical for numerous developmental and disease processes. A developmentally reiterated form of migration is radial intercalation; the process by which cells move in a direction orthogonal to the plane of the tissue from an inner layer to an outer layer. We use the radial intercalation of cells into the skin of Xenopus laevis embryos as a model to study directed cell migration within an epithelial tissue. We identify a novel function for both the microtubule-binding protein CLAMP and members of the microtubule-regulating Par complex during intercalation. Specifically, we show that Par3 and aPKC promote the apical positioning of centrioles, whereas CLAMP stabilizes microtubules along the axis of migration. We propose a model in which the Par complex defines the orientation of apical migration during intercalation and in which subcellular localization of CLAMP promotes the establishment of an axis of microtubule stability required for the active migration of cells into the outer epithelium.
CLA MP/Spef1 regulates planar cell polarity signaling and asymmetric microtubule accumulation in the Xenopus ciliated epithelia
JOURNAL OF CELL BIOLOGY
Authors: Kim, Sun K.; Zhang, Siwei; Werner, Michael E.; Brotslaw, Eva J.; Mitchell, Jennifer W.; Altabbaa, Mohamed M.; Mitchell, Brian J.
Abstract
Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell-cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity. We have identified CLA MP/Spef1 as a novel regulator of PCP signaling. In addition to decorating microtubules (MTs) and the ciliary rootlet, a pool of CLA MP localizes at the apical cell cortex. Depletion of CLA MP leads to the loss of PCP protein asymmetry, defects in cilia polarity, and defects in the angle of cell division. Additionally, depletion of CLA MP leads to a loss of the atypical cadherin-like molecule Celrs2, suggesting that CLA MP facilitates the stabilization of junctional interactions responsible for proper PCP protein localization. Depletion of CLA MP also affects the polarized organization of MTs. We hypothesize that CLA MP facilitates the establishment of cell polarity and promotes the asymmetric accumulation of MTs downstream of the establishment of proper PCP.