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果蝇 IgCAM 黏附受体与 Cd2ap/Cin85 同源物 cindr 之间的相互作用。

Interactions between Drosophila IgCAM adhesion receptors and cindr, the Cd2ap/Cin85 ortholog.

机构信息

Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York, USA.

出版信息

Dev Dyn. 2012 Dec;241(12):1933-43. doi: 10.1002/dvdy.23879. Epub 2012 Oct 29.

DOI:10.1002/dvdy.23879
PMID:23027549
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3677828/
Abstract

BACKGROUND

Morphogenetic modeling of tissues requires coordinated regulation of adhesion. For its correct patterning, the Drosophila pupal eye requires several Immunoglobulin superfamily cell adhesion molecules (IgCAMs) and the adaptor protein Cindr. Orthologs of these proteins are essential components of specialized junctions of the vertebrate kidney; the Cindr ortholog Cd2ap is essential for the integrity of this structure.

RESULTS

Reducing Cindr during fly eye development led to incorrect distribution of the IgCAMs Roughest (Rst) and Hibris (Hbs). Both bound Cindr. Disrupting endocytosis similarly led to Rst and Hbs mis-localization; our data suggests an additional early requirement for endocytosis in regulating Hbs localization or stability. Finally, Rst and Hbs localized correctly only when in stable membrane complexes and we propose that Cindr anchors these to the cytoskeleton. This regulation likely does not extend to IgCAMs Kin of irre (Kirre) and Sticks and stones (Sns) in the pupal eye; neither interacted with Cindr in in vitro assays. Nonetheless, Kirre and Sns partially mis-localized when Cindr was reduced, possibly due to interactions with Rst/Hbs.

CONCLUSIONS

Our data suggests Cindr recapitulates both proposed functions of its mammalian orthologs Cd2ap and Cin85: targeting the IgCAMs Rst and Hbs for endocytosis and stabilizing these heterophilic IgCAM complexes.

摘要

背景

组织形态发生模型需要协调调节粘附。为了正确的模式形成，果蝇蛹眼需要几种免疫球蛋白超家族细胞粘附分子（IgCAMs）和衔接蛋白 Cindr。这些蛋白质的同源物是脊椎动物肾脏特化连接的基本组成部分；Cindr 的同源物 Cd2ap 是该结构完整性所必需的。

结果

在蝇眼发育过程中降低 Cindr 会导致 IgCAMs Roughest（Rst）和 Hibris（Hbs）分布不正确。两者都与 Cindr 结合。内吞作用的破坏同样导致 Rst 和 Hbs 定位错误；我们的数据表明，内吞作用在调节 Hbs 定位或稳定性方面存在额外的早期需求。最后，只有当 Rst 和 Hbs 定位于稳定的膜复合物中时，它们才会正确定位，我们提出 Cindr 将这些锚定到细胞骨架上。这种调节可能不适用于蛹眼中的 IgCAMs Kin of irre（Kirre）和 Sticks and stones（Sns）；它们在体外实验中均未与 Cindr 相互作用。尽管如此，当 Cindr 减少时，Kirre 和 Sns 部分定位错误，可能是由于与 Rst/Hbs 的相互作用。

结论

我们的数据表明 Cindr 再现了其哺乳动物同源物 Cd2ap 和 Cin85 的两种拟议功能：将 IgCAMs Rst 和 Hbs 靶向内吞作用，并稳定这些异源 IgCAM 复合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/08d534669b0d/nihms-468764-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/858264460dc2/nihms-468764-f0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/3360be1538ad/nihms-468764-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/dd145db4e030/nihms-468764-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/d2464e8ced8a/nihms-468764-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/ae815b133ae4/nihms-468764-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/a8eab4d79415/nihms-468764-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/08d534669b0d/nihms-468764-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/858264460dc2/nihms-468764-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/c20e15971aa3/nihms-468764-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/9f3faee1da9e/nihms-468764-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/3360be1538ad/nihms-468764-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/dd145db4e030/nihms-468764-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/d2464e8ced8a/nihms-468764-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/ae815b133ae4/nihms-468764-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/a8eab4d79415/nihms-468764-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd7/3677828/08d534669b0d/nihms-468764-f0009.jpg

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