title: Mitotic internalization of planar cell polarity proteins preserves tissue polarity.
abstract: Planar cell polarity (PCP) is the collective polarization of cells along the epithelial plane, a process best understood in the terminally differentiated Drosophila wing. Proliferative tissues such as mammalian skin also show PCP, but the mechanisms that preserve tissue polarity during proliferation are not understood. During mitosis, asymmetrically distributed PCP components risk mislocalization or unequal inheritance, which could have profound consequences for the long-range propagation of polarity. Here, we show that when mouse epidermal basal progenitors divide PCP components are selectively internalized into endosomes, which are inherited equally by daughter cells. Following mitosis, PCP proteins are recycled to the cell surface, where asymmetry is re-established by a process reliant on neighbouring PCP. A cytoplasmic dileucine motif governs mitotic internalization of atypical cadherin Celsr1, which recruits Vang2 and Fzd6 to endosomes. Moreover, embryos transgenic for a Celsr1 that cannot mitotically internalize exhibit perturbed hair-follicle angling, a hallmark of defective PCP. This underscores the physiological relevance and importance of this mechanism for regulating polarity during cell division.
authors: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, New York 10065, USA.
authors: Danelle
authors: D
authors: Devenport
authors: Daniel
authors: D
authors: Oristian
authors: Evan
authors: E
authors: Heller
authors: Elaine
authors: E
authors: Fuchs
mesh_terms: D000818:Animals; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D048749:Cytokinesis / Q000502:physiology; D004705:Endocytosis; D011992:Endosomes / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D051157:Frizzled Receptors / Q000502:physiology; D007399:Interphase / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: C117380:Celsr1 protein, mouse; D051157:Frizzled Receptors; C111048:Fzd6 protein, mouse; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled