The tumor suppressor Lgl1 regulates front-rear polarity of migrating cells

Research output: Contribution to journalReview articlepeer-review

Abstract

Cell migration is a highly integrated, multistep process that plays an important role in physiological and pathological processes. The migrating cell is highly polarized, with complex regulatory pathways that integrate its component processes spatially and temporally.1 The Drosophila tumor suppressor, Lethal (2) giant larvae (Lgl), regulates apicalbasal polarity in epithelia and asymmetric cell division.2 But little is known about the role of Lgl in establishing cell polarity in migrating cells. Recently, we showed that the mammalian Lgl1 interacts directly with non-muscle myosin IIA (NMIIA), inhibiting its ability to assemble into filaments in vitro.3 Lgl1 also regulates the cellular localization of NMIIA, the maturation of focal adhesions, and cell migration.3 We further showed that phosphorylation of Lgl1 by aPKCz prevents its interaction with NMIIA and is important for Lgl1 and acto-NMII cytoskeleton cellular organization.4 Lgl is a critical downstream target of the Par6-aPKC cell polarity complex; we showed that Lgl1 forms two distinct complexes in vivo, Lgl1-NMIIA and Lgl1-Par6-aPKCz in different cellular compartments. 4 We further showed that aPKCz and NMIIA compete to bind directly to Lgl1 through the same domain. These data provide new insights into the role of Lgl1, NMIIA, and Par6-aPKCz in establishing front-rear polarity in migrating cells. In this commentary, I discuss the role of Lgl1 in the regulation of the acto-NMII cytoskeleton and its regulation by the Par6-aPKCz polarity complex, and how Lgl1 activity may contribute to the establishment of front-rear polarity in migrating cells.

Original languageAmerican English
Pages (from-to)378-383
Number of pages6
JournalCell Adhesion and Migration
Volume8
Issue number4
DOIs
StatePublished - 1 Jul 2014

Keywords

  • Cell migration
  • Cell polarity
  • Lethal giant larvae (Lgl)
  • Nonmuscle myosin II
  • Par6-aPKC

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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