TY - JOUR
T1 - Mitotic internalization of planar cell polarity proteins preserves tissue polarity
AU - Devenport, Danelle
AU - Oristian, Daniel
AU - Heller, Evan
AU - Fuchs, Elaine
N1 - Funding Information:
We thank N. Stokes for her assistance in the mouse facility, M. Montcouquoil for Vangl2 antibodies, and E. Vladar and J. Axelrod for sharing the lenti-Celsr1ΔN–GFP construct. We thank S. Simon laboratory members L. Macro and C. Atkinson for advice and constructs for TIRF imaging. We are grateful to S. Williams for retroviral vectors and technical assistance and to B. Short and members of the Fuchs laboratory for discussions and reading of the manuscript. We thank A. North and K. Thomas at the RU Bioimaging Resource Center for assistance with image acquisition, and the Comparative Biology Center (CBC) for their help in veterinary care. D.D. is the recipient of a K99 Award from the National Institutes of Health. E.F. is an investigator in the Howard Hughes Medical Institute. Work was supported by the Howard Hughes Medical Institute and the National Institutes of Health.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
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U2 - 10.1038/ncb2284
DO - 10.1038/ncb2284
M3 - Article
C2 - 21743464
AN - SCOPUS:79960996719
SN - 1465-7392
VL - 13
SP - 893
EP - 902
JO - Nature cell biology
JF - Nature cell biology
IS - 8
ER -