Clathrin phosphorylation is required for actin recruitment at sites of bacterial adhesion and internalization

Institut Pasteur, Unité des Interactions Bactéries-Cellules, Paris F-75015, France.
The Journal of Cell Biology (Impact Factor: 9.83). 10/2011; 195(3):525-36. DOI: 10.1083/jcb.201105152
Source: PubMed


Bacterial pathogens recruit clathrin upon interaction with host surface receptors during infection. Here, using three different infection models, we observed that host-pathogen interactions induce tyrosine phosphorylation of clathrin heavy chain. This modification was critical for recruitment of actin at bacteria-host adhesion sites during bacterial internalization or pedestal formation. At the bacterial interface, clathrin assembled to form coated pits of conventional size. Because such structures cannot internalize large particles such as bacteria, we propose that during infection, clathrin-coated pits serve as platforms to initiate actin rearrangements at bacteria-host adhesion sites. We then showed that the clathrin-actin interdependency is initiated by Dab2 and depends on the presence of clathrin light chain and its actin-binding partner Hip1R, and that the fully assembled machinery can recruit Myosin VI. Together, our study highlights a physiological role for clathrin heavy chain phosphorylation and reinforces the increasingly recognized function of clathrin in actin cytoskeletal organization in mammalian cells.

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Available from: Matteo Bonazzi
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    • "Receptor ubiquitination induces the recruitment of clathrin and other components of the endocytic machinery, leading to assembly of clathrin-coated pits, whose reduced size precludes bacterial compartmentalization into those pits. Instead, it is proposed that the clathrin lattices function as platforms for the recruitment of actin via the actin-binding protein Hip1R and for the recruitment of myosin VI, which drives bacterial internalization (Bonazzi et al., 2011). Together, InlA and InlB exploit E-cadherin-and Metmediated signalling pathways, as well as their recycling pathways, to cause actin polymerization at bacterial entry sites (Fig. 1). "
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    • "Based on these observations, we propose that underneath a phagocytic cup, CHC-1 oligomerizes into a scaffolding structure that facilitates actin remodeling. This structure might resemble the flat clathrin patches that coat specific membrane domains on endosomes or the trans-Golgi network (Young, 2007; Williams and Urbé, 2007), or the clathrin plaques that facilitate the entry of bacterial pathogens into non-phagocytic mammalian cells through organizing actin polymerization (Bonazzi et al., 2011). Our observations further suggest that, unlike in endocytosis, where actin primarily facilitates the invagination of clathrin-coated membrane and the generation of relatively small endocytic vesicles, during the engulfment of apoptotic cells, which are much larger (at least 3 μm), the clathrin-actin crosstalk not only induces membrane curvature, but, more importantly, directs actin polymerization and drives pseudopod extension around apoptotic cells. "
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