Drosophila Crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres

Abstract

Drosophila Crumbs (Crb) is required for apical–basal polarity and is an apical determinant in embryonic epithelia1,2. Here, we describe properties of Crb that control the position and integrity of the photoreceptor adherens junction and photosensitive organ, or rhabdomere3. In contrast to normal photoreceptor adherens junctions and rhabdomeres, which span the depth of the retina, adherens junctions and rhabdomeres of Crb-deficient photoreceptors initially accumulate at the top of the retina and fail to maintain their integrity as they stretch to the retinal floor. We show that Crb controls localization of the adherens junction through its intracellular domain containing a putative binding site for a protein 4.1 superfamily protein (FERM)4,5. Although loss of Crb or overexpression of the FERM binding domain causes mislocalization of adherens junctions, they do not result in a significant loss of photoreceptor polarity. Mutations in CRB1, a human homologue of crb, are associated with photoreceptor degeneration in retinitis pigmentosa 12 (RP12) and Leber congenital amaurosis (LCA)6,7,8,9,10. The intracellular domain of CRB1 behaves similarly to its Drosophila counterpart when overexpressed in the fly eye. Our studies may provide clues for mechanisms of photoreceptor degeneration in RP12 and LCA.

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Figure 1: Dlt and Crb are localized to the rhabdomere stalk.
Figure 2: crb photoreceptors fail to extend rhabdomeres and accumulate Arm distally.
Figure 3: crb photoreceptor AJs and rhabdomeres are mispositioned without loss of polarity.
Figure 4: Overexpression of CrbMyc–intra and human CRB1intra mislocalizes AJs and Dlt, leading to loss of cell polarity.
Figure 5: The juxtamembrane region of Crb is suffcient to recruit AJs independently of Dlt or polarity defects.

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Acknowledgements

We especially thank K.-O. Cho for her contribution to experimental design and for her support. We thank E. Knust for reagents and U. Tepass for discussion of unpublished results. We thank J. Chern and J. Lim for comments and discussion, B. Kehl and Z. H. Chen for technical assistance. We thank the Indiana Stock Center for providing flies. We thank H. Adams for technical assistance with TEM. Confocal microscopy was supported by a grant from the National Institutes of Health to D. B. Jones. S.I. and S.-C.N. are postdoctoral fellows. H.J.B. is a Howard Hughes Medical Institute Investigator. M.A.B. is supported by a Howard Temin Career Development Award from the National Cancer Institute. M.A.B., H.J.B., and K.-W.C. are supported by the NIH and K.-W.C. by the Retina Research Foundation.

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Correspondence to Kwang-Wook Choi.

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Izaddoost, S., Nam, S., Bhat, M. et al. Drosophila Crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres. Nature 416, 178–183 (2002). https://doi.org/10.1038/nature720

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