Singer-Krüger B, Nemoto Y, Daniell L, Ferro-Novick S, De Camilli P
Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, New Haven CT, USA.
J Cell Sci. 1998 Nov;111 ( Pt 22):3347-56. doi: 10.1242/jcs.111.22.3347.
The synaptojanins represent a subfamily of inositol 5'-phosphatases that contain an NH2-terminal Sac1p homology domain. A nerve terminal-enriched synaptojanin, synaptojanin 1, was previously proposed to participate in the endocytosis of synaptic vesicles and actin function. The genome of Saccharomyces cerevisiae contains three synaptojanin-like genes (SJL1, SJL2 and SJL3), none of which is essential for growth. We report here that a yeast mutant lacking SJL1 and SJL2 (Deltasjl1 Deltasjl2) exhibits a severe defect in receptor-mediated and fluid-phase endocytosis. A less severe endocytic defect is present in a Deltasjl2 Deltasjl3 mutant, while endocytosis is normal in a Deltasjl1 Deltasjl3 mutant. None of the mutants are impaired in invertase secretion. The severity of the endocytic impairment of the sjl double mutants correlates with the severity of actin and polarity defects. Furthermore, the deletion of SJL1 suppresses the temperature-sensitive growth defect of sac6, a mutant in yeast fimbrin, supporting a role for synaptojanin family members in actin function. These findings provide a first direct evidence for a role of synaptojanin family members in endocytosis and provide further evidence for a close link between endocytosis and actin function.
突触素代表了一个肌醇5'-磷酸酶亚家族，其包含一个NH2末端的Sac1p同源结构域。先前有人提出，一种在神经末梢中高度富集的突触素——突触素1，参与突触小泡的内吞作用和肌动蛋白功能。酿酒酵母的基因组包含三个类突触素基因（SJL1、SJL2和SJL3），其中没有一个对生长是必需的。我们在此报告，一个缺乏SJL1和SJL2的酵母突变体（Δsjl1 Δsjl2）在受体介导的内吞作用和液相内吞作用方面表现出严重缺陷。Δsjl2 Δsjl3突变体存在较轻微的内吞缺陷，而Δsjl1 Δsjl3突变体内吞作用正常。这些突变体在转化酶分泌方面均未受损。sjl双突变体内吞损伤的严重程度与肌动蛋白和极性缺陷的严重程度相关。此外，SJL1的缺失抑制了sac6（酵母丝束蛋白中的一个突变体）的温度敏感型生长缺陷，这支持了突触素家族成员在肌动蛋白功能中发挥作用。这些发现首次直接证明了突触素家族成员在内吞作用中的作用，并为内吞作用与肌动蛋白功能之间的紧密联系提供了进一步的证据。
