The intracellular bacteriumOrientia tsutsugamushihijacks the adaptor protein BICD2 for dynein-based motility

Author:

Manigrasso GiuliaORCID,Saharat KittiratORCID,Kullapanich ChitrasakORCID,Boulanger JeromeORCID,Morgan Tomos E.ORCID,Kramer HolgerORCID,Salje JeanneORCID,Carter Andrew P.ORCID

Abstract

ABSTRACTThe intracellular bacteriumOrientia tsutsugamushirelies on the microtubule cytoskeleton and the motor protein dynein to traffic to the perinuclear region within infected cells. However, it remains unclear how the bacterium is coupled to the dynein machinery and how transport is regulated. Here, we discover thatO. tsutsugamushiuses its autotransporter protein ScaC to recruit the dynein adaptor BICD2 to the bacterial surface. We show that ScaC is sufficient to engage dynein-based motility in the absence of other bacterial proteins and that BICD2 is required for efficient movement ofO. tsutsugamushiduring infection. Using TIRF single-molecule assays, we demonstrate that ScaC induces BICD2 to adopt an open conformation which activates the assembly of dynein-dynactin complexes. Our results reveal a novel role for BICD2 during bacterial infection and provide mechanistic insights into the life cycle of an important human pathogen.

Publisher

Cold Spring Harbor Laboratory

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