Actin pedestal formation by enteropathogenic Escherichia coli is regulated by IQGAP1, calcium, and calmodulin.
During infection, enteropathogenic Escherichia coli (EPEC) injects effector proteins into the host cell to manipulate the actin cytoskeleton and promote formation of actin pedestals. IQGAP1 is a multidomain protein that participates in numerous cellular functions, including Rac1/Cdc42 and Ca(2+)/calmodulin signaling and actin polymerization. Here we report that IQGAP1, Ca(2+), and calmodulin modulate actin pedestal formation by EPEC. Infection with EPEC promotes both the interaction of IQGAP1 with calmodulin and the localization of IQGAP1 and calmodulin to actin pedestals while reducing the interaction of IQGAP1 with Rac1 and Cdc42. IQGAP1-null fibroblasts display a reduced polymerization of actin in response to EPEC. In addition, antagonism of calmodulin or chelation of intracellular Ca(2+) reduces EPEC-dependent actin polymerization. Furthermore, IQGAP1 specifically interacts with Tir in vitro and in cells. Together these data identify IQGAP1, Ca(2+), and calmodulin as a novel signaling complex regulating actin pedestal formation by EPEC.
Brown
Matthew D
MD
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Thorn 530, Boston, Massachusetts 02115, USA.
Bry
Lynn
L
Li
Zhigang
Z
Sacks
David B
DB
D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000737:chemistry*; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
D000199:Actins; D002147:Calmodulin; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D002118:Calcium