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Tepass/Macmillan
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Crumbs (Crb) helps flies distinguish apical from basal in their epithelia. Now two new studies show that it is required for cell expansion independently of its specification of apical polarity. During cell expansion, the apical domain of photoreceptors elongates perpendicular to the apical–basal axis so that the domain can extend from the top to the bottom of the fly eye. The process may be conserved in humans, consistent with the recent finding that mutations in the human homologue, CRB1, lead to human retinitis pigmentosa.
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& Z( \8 `. `7 f5 o1 ]In the maturing fly eye, the apical domains and rhabdomeres (containing visual pigment) are in the center of each cluster of photoreceptor cells. The rhabdomere is linked by the stalk membrane to the adherens junctions (AJs), which separate the apical and basolateral membranes.
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The new studies by Ulrich Tepass (University of Toronto, Toronto, Canada) and colleagues and Kwang-Wook Choi (Baylor College of Medicine, Houston, TX) and colleagues demonstrate that the human and fly versions of Crumbs localize to corresponding domains of the apical plasma membrane in the stalk of the fly photoreceptor and the inner segment of mammalian photoreceptors. In this region, Crb appears to be carrying out two functions. First, it cements the AJs together so they form a continuous band from the top to the bottom of the eye. Crb is ideally suited for this job because, based on its function in determining cell polarity; it is already in the correct, apical part of the eye where the AJs are needed. Second, Crb contributes to the elongation of the rhabdomere during the rapid growth that drives expansion toward the base of the retina. Tepass hypothesizes that this may be a consequence of Crb binding a web of ?H-Spectrin, which then reduces the general level of endocytosis.: A( ]# |3 ]1 _/ O1 Y" v
$ s, n" A8 F0 X' _Overexpression of corresponding domains of fly Crb and human CRB1 had similar effects, suggesting that the function of the protein is conserved between the species, despite marked differences in the light receptors. Further study of the system in flies may provide clues about why the retinal degeneration seen in humans is a relatively slow process.
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References:
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Izaddoost, S., et al. 2002. Nature. 10.1038/nature720.8 A. l3 o1 B1 a7 l$ j3 i
0 q; ~8 t6 K' J: }; f- B/ H3 LPellikka, M., et al. 2002. Nature. 10.1038/nature721.(Growth of the photoreceptor stalk membra) |
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发表于 2009-3-6 00:18
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