LGL can partition the cortex of one-cell Caenorhabditis elegans embryos into two domains.
Many metazoan cell types are polarized by asymmetric partitioning of the conserved PAR (PAR-3/PAR-6/PKC-3) complex. Cortical domains containing this PAR complex are counterbalanced by opposing domains of varying composition. The tumor-suppressor protein LGL facilitates asymmetric localization of cell fate determinants, in part through modulating the activity of the PAR complex. However, the mechanisms by which LGL acts to maintain a cortical domain remain unclear. Here we identify Caenorhabditis elegans LGL in a biochemical complex with PAR proteins, which localize to the anterior cortex. But LGL itself localizes to the posterior cortex. We show that increasing the amounts of LGL can restrict localization of the PAR complex to an anterior cortical domain, even in the absence of PAR-2. Importantly, LGL must be phosphorylated on conserved residues to exert this function. LGL and the PAR complex can maintain two cortical domains that are sufficient to partition cell fate determinants. Our data suggest a mechanism of "mutual elimination" in which an LGL phosphorylation cycle regulates association of the PAR complex with the cortex: binding of LGL to the PAR complex at the interface of the two domains stimulates its phosphorylation by PKC-3, and the whole complex leaves the cortex.
Hoege
Carsten
C
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany. hoege@mpi-cbg.de
Constantinescu
Alexandru-Tudor
AT
Schwager
Anne
A
Goehring
Nathan W
NW
Kumar
Prateek
P
Hyman
Anthony A
AA
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D002970:Cleavage Stage, Ovum / Q000378:metabolism / Q000502:physiology*; D019295:Computational Biology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C553666:LGL-1 protein, C elegans; D046912:Multiprotein Complexes; D025521:Tumor Suppressor Proteins; C512642:par-6 protein, C elegans; D049452:Green Fluorescent Proteins; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C