Dorot Orly, Steller Hermann, Segal Daniel, Horowitz Mia
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
Howard Hughes Medical Institute, Strang Laboratory of Cancer Research, The Rockefeller University, New York, New York, United States of America.
PLoS One. 2017 Jan 6;12(1):e0169639. doi: 10.1371/journal.pone.0169639. eCollection 2017.
Endocytosis is a multi-step process involving a large number of proteins, both general factors, such as clathrin and adaptor protein complexes, and unique proteins, which modulate specialized endocytic processes, like the EHD proteins. EHDs are a family of Eps15 Homology Domain containing proteins that consists of four mammalian homologs, one C. elegans, one Drosophila melanogaster and two plants orthologs. These membrane-associated proteins are involved in different steps of endocytic trafficking pathways. We have previously shown that the Drosophila EHD ortholog, PAST1, associates predominantly with the plasma membrane. Mutations in Past1 result in defects in endocytosis, male sterility, temperature sensitivity and premature death of the flies. Also, Past1 genetically interacts with Notch. In the present study, we investigated the role of PAST1 in the developing fly eye. In mutant flies lacking PAST1, abnormal differentiation of photoreceptors R1, R6 and R7 was evident, with partial penetrance. Likewise, five cone cells were present instead of four. Expression of transgenic PAST1 resulted in a dominant negative effect, with a phenotype similar to that of the deletion mutant, and appearance of additional inter-ommatidial pigment cells. Our results strongly suggest a role for PAST1 in differentiation of photoreceptors R1/R6/R7 and cone cells of the fly ommatidia.
内吞作用是一个涉及大量蛋白质的多步骤过程,这些蛋白质既有一般因子,如网格蛋白和衔接蛋白复合物,也有独特的蛋白质,它们调节特殊的内吞过程,如EHD蛋白。EHD是一个包含Eps15同源结构域的蛋白质家族,由四个哺乳动物同源物、一个秀丽隐杆线虫同源物、一个黑腹果蝇同源物和两个植物直系同源物组成。这些膜相关蛋白参与内吞运输途径的不同步骤。我们之前已经表明,果蝇EHD直系同源物PAST1主要与质膜相关。Past1中的突变导致内吞作用缺陷、雄性不育、温度敏感性和果蝇过早死亡。此外,Past1与Notch发生遗传相互作用。在本研究中,我们研究了PAST1在果蝇发育中的眼睛中的作用。在缺乏PAST1的突变果蝇中,光感受器R1、R6和R7的异常分化很明显,具有部分外显率。同样,存在五个而不是四个视锥细胞。转基因PAST1 的表达产生了显性负效应,其表型与缺失突变体相似,并且出现了额外的小眼间色素细胞。我们的结果强烈表明PAST1在果蝇小眼的光感受器R1/R6/R7和视锥细胞的分化中起作用。