Functional analysis of Dictyostelium IBARa reveals a conserved role of the I-BAR domain in endocytosis.
Functional analysis of Dictyostelium IBARa reveals a conserved role of the I-BAR domain in endocytosis.
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DOI：
10.1042/bj20101684
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发表时间：
2011-05
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通讯作者：
Douwe M Veltman;Giulio Auciello;H. Spence;L. Machesky;J. Rappoport;R. Insall
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文献类型：
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作者：
Douwe M Veltman;Giulio Auciello;H. Spence;L. Machesky;J. Rappoport;R. Insall
I-BAR（inverse-Bin/amphiphysin/Rvs）结构域包含的蛋白质如IRSp 53（53 kDa的胰岛素受体底物）与向外弯曲的膜结合，并将它们连接到参与肌动蛋白动力学的蛋白质。对I-BAR蛋白的研究主要集中在丝状足和片状足的形成中可能的作用，但其完整的生理功能仍不清楚。社交阿米巴盘基网柄菌编码一种称为IBARa的单一I-BAR/SH 3（其中SH 3是Src同源性3）蛋白，以及与哺乳动物细胞中的IRSp 53家族蛋白相互作用的蛋白质的同源物，沿着，提供了研究其细胞功能的绝佳模型。IBARa编码基因的破坏导致发育的轻度缺陷，但丝状足和伪足动力学不受影响。此外，异位表达的IBARa不诱导丝状足形成，也不定位于丝状足。相反，IBARa在被内吞之前立即与网格蛋白斑点结合。这一作用是保守的：人BAIAP 2L 2（脑特异性血管生成抑制剂1相关蛋白2样2）也与网格蛋白斑紧密共定位，尽管其同系物IRSp 53和IRTKS（胰岛素受体酪氨酸激酶底物）与其它点状结构相关。本研究的结果表明，I-BAR蛋白质有助于产生胞吞作用所需的膜曲率，并意味着IRSp 53家族蛋白质在囊泡运输中的意想不到的作用。
I-BAR (inverse-Bin/amphiphysin/Rvs)-domain-containing proteins such as IRSp53 (insulin receptor substrate of 53 kDa) associate with outwardly curved membranes and connect them to proteins involved in actin dynamics. Research on I-BAR proteins has focussed on possible roles in filopod and lamellipod formation, but their full physiological function remains unclear. The social amoeba Dictyostelium encodes a single I-BAR/SH3 (where SH3 is Src homology 3) protein, called IBARa, along with homologues of proteins that interact with IRSp53 family proteins in mammalian cells, providing an excellent model to study its cellular function. Disruption of the gene encoding IBARa leads to a mild defect in development, but filopod and pseudopod dynamics are unaffected. Furthermore, ectopically expressed IBARa does not induce filopod formation and does not localize to filopods. Instead, IBARa associates with clathrin puncta immediately before they are endocytosed. This role is conserved: human BAIAP2L2 (brain-specific angiogenesis inhibitor 1-associated protein 2-like 2) also tightly co-localizes with clathrin plaques, although its homologues IRSp53 and IRTKS (insulin receptor tyrosine kinase substrate) associate with other punctate structures. The results from the present study suggest that I-BAR-containing proteins help generate the membrane curvature required for endocytosis and implies an unexpected role for IRSp53 family proteins in vesicle trafficking.