Basolateral targeting by leucine-rich repeat domains in epithelial cells.
The asymmetric distribution of proteins to basolateral and apical membranes is an important feature of epithelial cell polarity. To investigate how basolateral LAP proteins (LRR (for leucine-rich repeats) and PDZ (for PSD-95/Discs-large/ZO-1), which play key roles in cell polarity, reach their target membrane, we carried out a structure-function study of three LAP proteins: Caenorhabditis elegans LET-413, human Erbin and human Scribble (hScrib). Deletion and point mutation analyses establish that their LRR domain is crucial for basolateral membrane targeting. This property is specific to the LRR domain of LAP proteins, as the non-LAP protein SUR-8 does not localize at the basolateral membrane of epithelial cells, despite having a closely related LRR domain. Importantly, functional studies of LET-413 in C. elegans show that although its PDZ domain is dispensable during embryogenesis, its LRR domain is essential. Our data establish a novel paradigm for protein localization by showing that a subset of LRR domains direct subcellular localization in polarized cells.
[1] Centre de Génétique Moléculaire, CNRS, Avenue de la terrasse-Batiment 26, 91198 Gif-sur-Yvette Cedex, France. legouis@cgm.cnrs-gif.fr
Renaud
R
Legouis
Fanny
F
Jaulin-Bastard
Sonia
S
Schott
Christel
C
Navarro
Jean-Paul
JP
Borg
Michel
M
Labouesse
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein; D004847:Epithelial Cells / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D000090263:Leucine-Rich Repeat Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; C413362:LET-413 protein, C elegans; D000090263:Leucine-Rich Repeat Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011506:Proteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C033652:postsynaptic density proteins