A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis
A novel dynamin-associating molecule, formin-binding protein 17, induces tubular membrane invaginations and participates in endocytosis
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DOI：
10.1074/jbc.m404899200
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发表时间：
2004-09-17
影响因子：
4.8
通讯作者：
Mochizuki, N
中科院分区：
文献类型：
--
作者：
Kamioka, Y;Fukuhara, S;Mochizuki, N
发动蛋白通过C-末端富含脯氨酸的基序与多种含有SH 3结构域的分子相关联，并与它们一起参与内吞过程。在这里，我们研究了一种新的动力蛋白相关分子，形成蛋白结合蛋白17（FBP 17），参与变形质膜和内吞作用。FBP 17形成源自质膜的管状内陷。其N端Fer/CIP 4同源结构域、卷曲螺旋结构域和富含脯氨酸的基序是肾小管内陷和自组装所必需的，通过这些结构域可以诱导肾小管内陷。使用抗FBP 17抗体，我们在睾丸中检测到仅限于生殖细胞的阳性免疫反应。我们还通过免疫印迹和原位杂交检测了脑中的FBP 17。当COS细胞表达增强的绿色荧光蛋白标记的FBP 17与荧光标记的转铁蛋白，表皮生长因子，和霍乱毒素孵育，这些分子共定位与FBP 17诱导的肾小管内陷，这表明FBP 17是参与动力蛋白介导的内吞在网格蛋白依赖性和非依赖性的方式。因此，这些观察结果表明，FBP 17与发动蛋白相互作用，并通过形成囊泡管结构来调节内吞作用。
Dynamin associates with a variety of SH3 domain-containing molecules via a C-terminal proline-rich motif and takes part, with them, in endocytic processes. Here, we have investigated a new dynamin-associating molecule, formin-binding protein 17 (FBP17), involved in deforming the plasma membrane and in endocytosis. FBP17 formed tubular invaginations originating from the plasma membrane. Its N-terminal Fer/CIP4 homology domain, a coiled-coil domain, and a proline-rich motif were required for tubular invagination and self-assembly, by which tubular invagination might be induced. Using anti-FBP17 antibody, we detected positive immunoreactions in the testis that were restricted to the germ cells. We also detected FBP17 in the brain by immunoblotting and in situ hybridization. When COS cells expressing enhanced green fluorescent protein-tagged FBP17 were incubated with fluorescently labeled transferrin, epidermal growth factor, and cholera toxin, these molecules co-localized with FBP17-induced tubular invaginations, suggesting that FBP17 is involved in dynamin-mediated endocytosis in both a clathrin-dependent and -independent manner. These observations therefore indicate that FBP17 interacts with dynamin and regulates endocytosis by forming vesicotubular structures.