Scribble (Scrib) and Lethal giant larvae 1 (Lgl1) are conserved polarity proteins that play important roles in different forms of cell polarity. The roles of Scrib and Lgl1 in apical-basal cell polarity have been studied extensively, but little is known about their roles in the cell polarity of migrating cells. Furthermore, the effect of Scrib and Lgl1 interaction on cell polarity is largely unknown. In this study, we show that Scrib, through its leucine-rich repeat domain, forms a complex in vivo with Lgl1. Scrib also forms a complex with myosin II, and Scrib, Lgl1, and myosin II colocalize at the leading edge of migrating cells. The cellular localization and the cytoskeletal association of Scrib and Lgl1 are interdependent, as depletion of either protein affects its counterpart. In addition, depletion of either Scrib or Lgl1 disrupts the cellular localization of myosin II. We show that depletion of either Scrib or Lgl1 affects cell adhesion through the inhibition of focal adhesion disassembly. Finally, we show that Scrib and Lgl1 are required for proper cell polarity of migrating cells. These results provide new insights into the mechanism regulating the cell polarity of migrating cells by Scrib, Lgl1, and myosin II.
Bibliographical noteFunding Information:
We thank Tony Pawson (Mount Sinai Hospital, Toronto, Canada) for the Lgl1 construct, Patrick Humbert and Helena Richardson (La Trobe University, Melbourne, Australia) for Scrib constructs, Robert S. Adel-stein for NMII constructs, and Yael Feinstein Rotkopf for technical assistance with the microscopy work. This study was supported by the Israel Science Foundation (Grant No. 745/17), Israel Cancer Research Foundation, and Israel Cancer Association (Grant No. 20140082). S.R. holds the Daniel G. Miller Chair in Cancer Research.
© 2020 Abedrabbo and Ravid. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution-Noncommercial-Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).