Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis

Abstract

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.

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Figure 1: Distribution of Crb and CRB1 in PRCs.
Figure 2: Adult crb mutant eye phenotype.
Figure 3: Development of ZA defects in crb mutant PRCs.
Figure 4: Quantification of stalk length and ZA integrity in crb and kst mutant eyes.
Figure 5: Crb overexpression increases the length of the stalk membrane.
Figure 6: Crb interacts with βH-Spectrin.

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Acknowledgements

We are grateful to H. Hong and R. Derrane for technical assistance. We thank I. Dworkin for advice on statistical analysis. We thank H. Okano, the Developmental Studies Hybridoma Bank, and the Bloomington Drosophila Stock Center for reagents. We thank A. Satoh for permission to use the micrograph in Fig. 1g. We are grateful to S. Izaddoost and K.-W. Choi for discussing results before publication. We thank D. Godt, H. Lipshitz and E. Larsen for their comments on the manuscript. This work was supported by grants from the Canadian Institute of Health Research (to U.T.), the National Cancer Institute of Canada (to C.J.M.), and the National Institute of Health (to D.F.R.).

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Correspondence to Ulrich Tepass.

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Pellikka, M., Tanentzapf, G., Pinto, M. et al. Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis. Nature 416, 143–149 (2002). https://doi.org/10.1038/nature721

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