TY - JOUR
T1 - Combover/CG10732, a novel PCP effector for drosophila wing hair formation
AU - Fagan, Jeremy K.
AU - Dollar, Gretchen
AU - Lu, Qiuheng
AU - Barnett, Austen
AU - Jorge, Joaquin Pechuan
AU - Schlosser, Andreas
AU - Pfleger, Cathie
AU - Adler, Paul
AU - Jenny, Andreas
N1 - Funding Information:
Funding provided by National Institutes of Health (NIH) grant GM088202 (to AJ), NIH 5 T32 GM007491-35 (to JKF; PI Kielian), NIH GM037163 (to PNA), NIH R01CA140451(to CP), DOD W81XWH-14-1-0059 (to CP) and NSF 1257939 (to CP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are very grateful to Drs. M. Mlodzik (Mount Sinai, New York, NY), L. Luo (Stanford University, CA), B. Morrow, F. Marlow (both Albert Einstein College of Medicine, Bronx, NY), H. Huang and Y. Hong (U. Pittsburgh School of Medicine, Pittsburgh, PA) and the Bloomington and Vienna stock centers for fly stocks, plasmids and advice. We also would like to thank the BDGP and DGRC for plasmids, the Einstein Macromolecular Therapeutics Facility for antigen purification, and Drs. N. Baker and J. Secombe for comments on the manuscript. Special thanks to M. Mlodizk for initial support of the Rok screen. Data in this paper are from a thesis to be submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in the Graduate Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - The polarization of cells is essential for the proper functioning of most organs. Planar Cell Polarity (PCP), the polarization within the plane of an epithelium, is perpendicular to apical-basal polarity and established by the non-canonical Wnt/Fz-PCP signaling pathway. Within each tissue, downstream PCP effectors link the signal to tissue specific readouts such as stereocilia orientation in the inner ear and hair follicle orientation in vertebrates or the polarization of ommatidia and wing hairs in Drosophila melanogaster. Specific PCP effectors in the wing such as Multiple wing hairs (Mwh) and Rho Kinase (Rok) are required to position the hair at the correct position and to prevent ectopic actin hairs. In a genome-wide screen in vitro, we identified Combover (Cmb)/CG10732 as a novel Rho kinase substrate. Overexpression of Cmb causes the formation of a multiple hair cell phenotype (MHC), similar to loss of rok and mwh. This MHC phenotype is dominantly enhanced by removal of rok or of other members of the PCP effector gene family. Furthermore, we show that Cmb physically interacts with Mwh, and cmb null mutants suppress the MHC phenotype of mwh alleles. Our data indicate that Cmb is a novel PCP effector that promotes to wing hair formation, a function that is antagonized by Mwh.
AB - The polarization of cells is essential for the proper functioning of most organs. Planar Cell Polarity (PCP), the polarization within the plane of an epithelium, is perpendicular to apical-basal polarity and established by the non-canonical Wnt/Fz-PCP signaling pathway. Within each tissue, downstream PCP effectors link the signal to tissue specific readouts such as stereocilia orientation in the inner ear and hair follicle orientation in vertebrates or the polarization of ommatidia and wing hairs in Drosophila melanogaster. Specific PCP effectors in the wing such as Multiple wing hairs (Mwh) and Rho Kinase (Rok) are required to position the hair at the correct position and to prevent ectopic actin hairs. In a genome-wide screen in vitro, we identified Combover (Cmb)/CG10732 as a novel Rho kinase substrate. Overexpression of Cmb causes the formation of a multiple hair cell phenotype (MHC), similar to loss of rok and mwh. This MHC phenotype is dominantly enhanced by removal of rok or of other members of the PCP effector gene family. Furthermore, we show that Cmb physically interacts with Mwh, and cmb null mutants suppress the MHC phenotype of mwh alleles. Our data indicate that Cmb is a novel PCP effector that promotes to wing hair formation, a function that is antagonized by Mwh.
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U2 - 10.1371/journal.pone.0107311
DO - 10.1371/journal.pone.0107311
M3 - Article
C2 - 25207969
AN - SCOPUS:84945957114
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 9
M1 - e107311
ER -