The tumor suppressor Lgl1 regulates NMII-A cellular distribution and focal adhesion morphology to optimize cell migration.
The Drosophila tumor suppressor Lethal (2) giant larvae (Lgl) regulates the apical-basal polarity in epithelia and asymmetric cell division. However, little is known about the role of Lgl in cell polarity in migrating cells. In this study we show direct physiological interactions between the mammalian homologue of Lgl (Lgl1) and the nonmuscle myosin II isoform A (NMII-A). We demonstrate that Lgl1 and NMII-A form a complex in vivo and provide data that Lgl1 inhibits NMII-A filament assembly in vitro. Furthermore, depletion of Lgl1 results in the unexpected presence of NMII-A in the cell leading edge, a region that is not usually occupied by this protein, suggesting that Lgl1 regulates the cellular localization of NMII-A. Finally, we show that depletion of Lgl1 affects the size and number of focal adhesions, as well as cell polarity, membrane dynamics, and the rate of migrating cells. Collectively these findings indicate that Lgl1 regulates the polarity of migrating cells by controlling the assembly state of NMII-A, its cellular localization, and focal adhesion assembly.
Department of Biochemistry and Molecular Biology, Institute of Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Inbal
I
Dahan
Ahuv
A
Yearim
Yarin
Y
Touboul
Shoshana
S
Ravid
D000818:Animals; D019556:COS Cells; D002465:Cell Movement; D016764:Cell Polarity; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D022001:Focal Adhesions / Q000378:metabolism* / Q000648:ultrastructure; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D011487:Protein Conformation; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; C082939:Llgl1 protein, mouse; D025521:Tumor Suppressor Proteins; D024507:Nonmuscle Myosin Type IIA