Evolution and cell physiology. 3. Using Dictyostelium discoideum to investigate mechanisms of epithelial polarity.
In Metazoa, a polarized epithelium forms a single-cell-layered barrier that separates the outside from the inside of the organism. In tubular epithelia, the apical side of the cell is constricted relative to the basal side, forming a wedge-shaped cell that can pack into a tube. Apical constriction is mediated by actomyosin activity. In higher animals, apical actomyosin is connected between cells by specialized cell-cell junctions that contain a classical cadherin, the Wnt signaling protein β-catenin, and the actin-binding protein α-catenin. The molecular mechanisms that lead to selective accumulation of myosin at the apical surface of cells are poorly understood. We found that the nonmetazoan Dictyostelium discoideum forms a polarized epithelium that surrounds the stalk tube at the tip of the multicellular fruiting body. Although D. discoideum lacks a cadherin homolog, it expresses homologs of β- and α-catenin. Both catenins are essential for formation of the tip epithelium, polarized protein secretion, and proper multicellular morphogenesis. Myosin localizes apically in tip epithelial cells, and it appears that constriction of this epithelial tube is required for proper morphogenesis. Localization of myosin II is controlled by the protein IQGAP1 and its binding partners cortexillins I and II, which function downstream of α- and β-catenin to exclude myosin from the basolateral cortex and promote apical accumulation of myosin. These studies show that the function of catenins in cell polarity predates the evolution of Wnt signaling and classical cadherins, and that apical localization of myosin is a morphogenetic mechanism conserved from nonmetazoans to vertebrates.
Program in Cancer Biology, Stanford University, Stanford, California;
William I
WI
Weis
W James
WJ
Nelson
Daniel J
DJ
Dickinson
D000818:Animals; D002468:Cell Physiological Phenomena / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D019143:Evolution, Molecular; D006801:Humans
apical constriction; catenins; cell polarity; epithelium; evolution