Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Nat Commun. 2021 Aug 4;12(1):4707. doi: 10.1038/s41467-021-24983-z.
Salmonella utilizes translocated virulence proteins (termed effectors) to promote host cell invasion. The effector SopD contributes to invasion by promoting scission of the plasma membrane, generating Salmonella-containing vacuoles. SopD is expressed in all Salmonella lineages and plays important roles in animal models of infection, but its host cell targets are unknown. Here we show that SopD can bind to and inhibit the small GTPase Rab10, through a C-terminal GTPase activating protein (GAP) domain. During infection, Rab10 and its effectors MICAL-L1 and EHBP1 are recruited to invasion sites. By inhibiting Rab10, SopD promotes removal of Rab10 and recruitment of Dynamin-2 to drive scission of the plasma membrane. Together, our study uncovers an important role for Rab10 in regulating plasma membrane scission and identifies the mechanism used by a bacterial pathogen to manipulate this function during infection.
沙门氏菌利用易位的毒力蛋白（称为效应物）促进宿主细胞入侵。效应物 SopD 通过促进质膜分裂来促进沙门氏菌包含的空泡的形成，从而促进入侵。SopD 在所有沙门氏菌谱系中表达，并在感染的动物模型中发挥重要作用，但它的宿主细胞靶标尚不清楚。在这里，我们表明 SopD 可以通过 C 末端 GTP 酶激活蛋白 (GAP) 结构域与小 GTP 酶 Rab10 结合并抑制其活性。在感染过程中，Rab10 及其效应物 MICAL-L1 和 EHBP1 被招募到入侵部位。通过抑制 Rab10，SopD 促进 Rab10 的去除和 Dynamin-2 的募集，从而驱动质膜的分裂。总之，我们的研究揭示了 Rab10 在调节质膜分裂中的重要作用，并确定了细菌病原体在感染过程中操纵这一功能的机制。
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