FERM protein EPB41L5 is a novel member of the mammalian CRB-MPP5 polarity complex.
Cell polarity is induced and maintained by separation of the apical and basolateral domains through specialized cell-cell junctions. The Crumbs protein and its binding partners are involved in formation and stabilization of adherens junctions. In this study, we describe a novel component of the mammalian Crumbs complex, the FERM domain protein EPB41L5, which associates with the intracellular domains of all three Crumbs homologs through its FERM domain. Surprisingly, the same FERM domain is involved in binding to the HOOK domain of MPP5/PALS1, a previously identified interactor of Crumbs. Co-expression and co-localization studies suggested that in several epithelial derived tissues Epb4.1l5 interacts with at least one Crumbs homolog, and with Mpp5. Although at early embryonic stages Epb4.1l5 is found at the basolateral membrane compartment, in adult tissues it co-localizes at the apical domain with Crumbs proteins and Mpp5. Overexpression of Epb4.1l5 in polarized MDCK cells affects tightness of cell junctions and results in disorganization of the tight junction markers ZO-1 and PATJ. Our results emphasize the importance of a conserved Crumbs-MPP5-EPB41L5 polarity complex in mammals.
Gosens
Ilse
I
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 10, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Sessa
Alessandro
A
den Hollander
Anneke I
AI
Letteboer
Stef J F
SJ
Belloni
Valentina
V
Arends
Maarten L
ML
Le Bivic
André
A
Cremers
Frans P M
FP
Broccoli
Vania
V
Roepman
Ronald
R
D000818:Animals; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology; D004285:Dogs; D004622:Embryo, Mammalian; D005136:Eye Proteins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000502:physiology; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection
C448939:CRB1 protein, human; C472002:CRB3 protein, human; D003598:Cytoskeletal Proteins; C525177:EPB41L5 protein, human; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D009703:Nucleoside-Phosphate Kinase; C501307:MPP5 protein, human; C499979:Mpp5 protein, mouse