TheC. eleganshomolog ofDrosophilaLethal giant larvae functions redundantly with PAR-2 to maintain polarity in the early embryo

Abstract

SUMMARYPolarity is essential for generating cell diversity. The one-cell C. elegans embryo serves as a model for studying the establishment and maintenance of polarity. In the early embryo, a myosin II-dependent contraction of the cortical meshwork asymmetrically distributes the highly conserved PDZ proteins PAR-3 and PAR-6, as well as an atypical protein kinase C (PKC-3), to the anterior. The RING-finger protein PAR-2 becomes enriched on the posterior cortex and prevents these three proteins from returning to the posterior. In addition to the PAR proteins, other proteins are required for polarity in many metazoans. One example is the conserved Drosophila tumor-suppressor protein Lethal giant larvae (Lgl). In Drosophila and mammals, Lgl contributes to the maintenance of cell polarity and plays a role in asymmetric cell division. We have found that the C. elegans homolog of Lgl, LGL-1, has a role in polarity but is not essential. It localizes asymmetrically to the posterior of the early embryo in a PKC-3-dependent manner, and functions redundantly with PAR-2 to maintain polarity. Furthermore, overexpression of LGL-1 is sufficient to rescue loss of PAR-2 function.LGL-1 negatively regulates the accumulation of myosin (NMY-2) on the posterior cortex, representing a possible mechanism by which LGL-1 might contribute to polarity maintenance.

Elaborating polarity: PAR proteins and the cytoskeleton

“…Two recent reports show that the conserved WD-repeat protein LGL-1 [a homolog of Lethal giant larvae (Lgl)] functions redundantly with PAR-2 to keep anterior PAR proteins from returning to the posterior cortex during the maintenance phase (Beatty et al, 2010;Hoege et al, 2010). Although lgl-1 mutant C. elegans embryos polarize, overexpressing LGL-1-GFP suppresses the polarity maintenance defects of par-2 mutants, and lgl-1 mutants are hypersensitive to PAR-2 depletion.…”

“…Although it is not known how LGL-1 facilitates polarity maintenance, LGL-1 homologs have been shown to bind myosin (Strand et al, 1994), and myosin levels are increased at the posterior cortex in lgl-1 par-2 double mutants (Beatty et al, 2010).…”

PAR-2, LGL-1 and the CDC-42 GAP CHIN-1 act in distinct pathways to maintain polarity in the C. elegans embryo

“…homolog of the Drosophila tumor suppressor protein Lethal Giant Larvae, was found to localize asymmetrically to the posterior cortex and function redundantly with PAR-2 to maintain polarity (Beatty et al, 2010;Hoege et al, 2010). LGL-1 is not required for polarity maintenance, but lgl-1; par-2 double mutants have a stronger phenotype than par-2 alone.…”

“…In par-2 mutants, the anterior PARs expand into the posterior but retain a graded distribution there. In lgl-1;par-2 double mutants, the anterior PAR proteins become even more symmetric, although reduced levels of anterior PARs are still apparent in the extreme posterior (Beatty et al, 2010). Although it is clear that PAR-2 and LGL-1 act in polarity maintenance, the molecular mechanisms by which the proteins function are not well understood.…”

Refining the role of Lgl, Dlg and Scrib in Tumor Suppression and Beyond: Learning from the Old Time Classics

“…The role of Lgl and the Par-complex was also analyzed in the polarity establishment of the early C. elegans embryo, where they maintain two cortical domains which are sufficient to partition cell fate determinants in the C. elegans embryo, by a mechanism of "mutual exclusion" (Hoege et al 2010). Lgl1 interacts with Par-2 in the posterior of the embryo, but Lgl1 can also compensate the function of Par-2 and restrict the anterior localization of the Par-complex, through a mechanism that involves Lgl phosphorylation (Hoege et al 2010) and a negative regulation of non-muscle myosin-II at the posterior cortex (Beatty, Morton and Kemphues 2010) Of particular interest are studies that relate the adenomatous polyposis coli (APC) tumour suppressor to the mammalian Dlg homologues. Dlg1 was isolated in a yeast-two-hybrid screen and was found to directly interact with APC , Ishidate et al 2000.…”