Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, England, UK.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
J Cell Biol. 2020 Oct 5;219(10). doi: 10.1083/jcb.201906021.
A subset of peroxisomes is retained at the mother cell cortex by the Pex3-Inp1 complex. We identify Inp1 as the first known plasma membrane-peroxisome (PM-PER) tether by demonstrating that Inp1 meets the predefined criteria that a contact site tether protein must adhere to. We show that Inp1 is present in the correct subcellular location to interact with both the plasma membrane and peroxisomal membrane and has the structural and functional capacity to be a PM-PER tether. Additionally, expression of artificial PM-PER tethers is sufficient to restore retention in inp1Δ cells. We show that Inp1 mediates peroxisome retention via an N-terminal domain that binds PI(4,5)P2 and a C-terminal Pex3-binding domain, forming a bridge between the peroxisomal membrane and the plasma membrane. We provide the first molecular characterization of the PM-PER tether and show it anchors peroxisomes at the mother cell cortex, suggesting a new model for peroxisome retention.
一组过氧化物酶体通过 Pex3-Inp1 复合物保留在母细胞皮层。我们将 Inp1 鉴定为第一个已知的质膜-过氧化物酶体 (PM-PER) 连接蛋白，通过证明 Inp1 符合接触部位连接蛋白必须遵守的预定标准。我们表明，Inp1 存在于与质膜和过氧化物酶体膜相互作用的正确亚细胞位置，并且具有成为 PM-PER 连接蛋白的结构和功能能力。此外，表达人工 PM-PER 连接蛋白足以恢复 inp1Δ 细胞的保留。我们表明，Inp1 通过与 PI(4,5)P2 结合的 N 端结构域和 C 端 Pex3 结合结构域介导过氧化物酶体的保留，在过氧化物酶体膜和质膜之间形成桥梁。我们提供了 PM-PER 连接蛋白的第一个分子特征，并表明它将过氧化物酶体锚定在母细胞皮层，这表明过氧化物酶体的保留有了一个新的模型。
