The cytoskeletal scaffold Shank3 is recruited to pathogen-induced actin rearrangements.
The common gastrointestinal pathogens enteropathogenic Escherichia coli (EPEC) and Salmonella typhimurium both reorganize the gut epithelial cell actin cytoskeleton to mediate pathogenesis, utilizing mimicry of the host signaling apparatus. The PDZ domain-containing protein Shank3, is a large cytoskeletal scaffold protein with known functions in neuronal morphology and synaptic signaling, and is also capable of acting as a scaffolding adaptor during Ret tyrosine kinase signaling in epithelial cells. Using immunofluorescent and functional RNA-interference approaches we show that Shank3 is present in both EPEC- and S. typhimurium-induced actin rearrangements and is required for optimal EPEC pedestal formation. We propose that Shank3 is one of a number of host synaptic proteins likely to play key roles in bacteria-host interactions.
Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Alan
A
Huett
John M
JM
Leong
Daniel K
DK
Podolsky
Ramnik J
RJ
Xavier
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D000818:Animals; D001422:Bacterial Adhesion; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology*; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology; D012486:Salmonella typhimurium / Q000502:physiology*; D015398:Signal Transduction
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C078332:Nck protein; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; C492357:SHANK3 protein, human