Abstract
Polarized epithelia develop distinct cell surface domains, with the apical membrane acquiring characteristic morphological features such as microvilli. Cell polarization is driven by polarity determinants including the evolutionarily conserved partitioning-defective (PAR) proteins that are separated into distinct cortical domains. PAR protein segregation is thought to be a consequence of asymmetric actomyosin contractions. The mechanism of activation of apically polarized actomyosin contractility is unknown. Here we show that the Cdc42 effector MRCK activates myosin-II at the apical pole to segregate aPKC-Par6 from junctional Par3, defining the apical domain. Apically polarized MRCK-activated actomyosin contractility is reinforced by cooperation with aPKC-Par6 downregulating antagonistic RhoA-driven junctional actomyosin contractility, and drives polarization of cytosolic brush border determinants and apical morphogenesis. MRCK-activated polarized actomyosin contractility is required for apical differentiation and morphogenesis in vertebrate epithelia and Drosophila photoreceptors. Our results identify an apical origin of actomyosin-driven morphogenesis that couples cytoskeletal reorganization to PAR polarity signalling.
MeSH terms
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Actomyosin / metabolism
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Animals, Genetically Modified
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Caco-2 Cells
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Cell Cycle Proteins / metabolism
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Cell Differentiation
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Cell Membrane / enzymology*
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Cell Polarity*
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Dogs
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Drosophila melanogaster / cytology
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Drosophila melanogaster / enzymology
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Epithelial Cells / enzymology*
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Genotype
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Guanine Nucleotide Exchange Factors / metabolism
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Humans
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Madin Darby Canine Kidney Cells
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Membrane Proteins / metabolism
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Morphogenesis
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Myosin Type II / metabolism
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Myotonin-Protein Kinase / genetics
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Myotonin-Protein Kinase / metabolism*
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Phenotype
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Photoreceptor Cells, Invertebrate / enzymology
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Protein Kinase C / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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RNA Interference
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Signal Transduction
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Time Factors
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Transfection
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cdc42 GTP-Binding Protein / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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Drosophila Proteins
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Guanine Nucleotide Exchange Factors
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Membrane Proteins
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PARD3 protein, human
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PARD6A protein, human
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Actomyosin
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Gek protein, Drosophila
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Myotonin-Protein Kinase
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Protein Serine-Threonine Kinases
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PKC-3 protein
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Protein Kinase C
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Myosin Type II
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cdc42 GTP-Binding Protein