PDF(Pubmed)
Abstract：
Src homology 3-domain growth factor receptor-bound 2-like interacting protein 1 (SGIP1), originally known as a regulator of energy homeostasis, was later found to be an ortholog of Fer/Cip4 homology domain-only (FCHo) proteins and to function during endocytosis. SGIP1α is a longer splicing variant in mouse brains that contains additional regions in the membrane phospholipid-binding domain (MP) and C-terminal region, but functional consequences with or without additional regions between SGIP1 and SGIP1α remain elusive. Moreover, many previous studies have either inadvertently used SGIP1 instead of SGIP1α or used the different isoforms with or without additional regions indiscriminately, resulting in further confusion. Here, we report that the additional region in the MP is essential for SGIP1α to deform membrane into tubules and for homo-oligomerization, and SGIP1, which lacks this region, fails to perform these functions. Moreover, only SGIP1α rescued endocytic defects caused by FCHo knock-down. Thus, our results indicate that SGIP1α, but not SGIP1, is the functional ortholog of FCHos, and SGIP1 and SGIP1α are not functionally redundant. These findings suggest that caution should be taken in interpreting the role of SGIP1 in endocytosis.
摘要：
Src同源性3结构域生长因子受体结合2样相互作用蛋白1（SGIP1），最初被称为能量稳态的调节器，后来发现是仅Fer/Cip4同源结构域（FCHo）蛋白的直系同源物，并在胞吞过程中起作用。SGIP1α是小鼠大脑中更长的剪接变体，在膜磷脂结合域（MP）和C末端区域中包含其他区域，但是在SGIP1和SGIP1α之间有或没有其他区域的功能后果仍然难以捉摸。此外，许多以前的研究要么无意中使用SGIP1代替SGIP1α，要么不加选择地使用不同的同工型，有或没有额外的区域，造成进一步的混乱。这里,我们报告说，在MP的额外区域是必不可少的SGIP1α膜变形为小管和同源寡聚化，和SGIP1，缺乏这个区域，无法执行这些功能。此外，只有SGIP1α挽救了由FCHo击倒引起的内吞缺陷。因此，我们的结果表明，SGIP1α，但不是SGIP1，是FCHos的功能直系同源，和SGIP1和SGIP1α在功能上不是冗余的。这些发现表明，在解释SGIP1在内吞作用中的作用时应谨慎。
