Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis.
The apical transmembrane protein Crumbs is a central regulator of epithelial apical-basal polarity in Drosophila. Loss-of-function mutations in the human homologue of Crumbs, CRB1 (RP12), cause recessive retinal dystrophies, including retinitis pigmentosa. Here we show that Crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. These subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila Crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity. We propose that Crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. Defects in such scaffolds may contribute to human CRB1-related retinal dystrophies.
Pellikka
Milena
M
Department of Zoology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.
Tanentzapf
Guy
G
Pinto
Madalena
M
Smith
Christian
C
McGlade
C Jane
CJ
Ready
Donald F
DF
Tepass
Ulrich
U
D022005:Adherens Junctions / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000648:ultrastructure; D005136:Eye Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D017385:Sequence Homology; D013049:Spectrin / Q000378:metabolism
C448939:CRB1 protein, human; D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C064360:crb protein, Drosophila; D013049:Spectrin