Bacterial actin assembly requires toca-1 to relieve N-wasp autoinhibition.
Actin polymerization in the mammalian cytosol can be locally activated by mechanisms that relieve the autoinhibited state of N-WASP, an initiator of actin assembly, a process that also requires the protein Toca-1. Several pathogenic bacteria, including Shigella, exploit this host feature to infect and disseminate efficiently. The Shigella outer membrane protein IcsA recruits N-WASP, which upon activation at the bacterial surface mediates localized actin polymerization. The molecular role of Toca-1 in N-WASP activation during physiological or pathological actin assembly processes in intact mammalian cells remains unclear. We show that actin tail initiation by S. flexneri requires Toca-1 for the conversion of N-WASP from a closed inactive conformation to an open active one. While N-WASP recruitment is dependent on IcsA, Toca-1 recruitment is instead mediated by S. flexneri type III secretion effectors. Thus, S. flexneri independently hijacks two nodes of the N-WASP actin assembly pathway to initiate localized actin tail assembly.
Leung
Yiuka
Y
Department of Medicine, Division of Infectious Diseases, Massachusetts General Hospital, Cambridge, MA 02139, USA.
Ally
Shabeen
S
Goldberg
Marcia B
MB
D000199:Actins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D009068:Movement; D011108:Polymers / Q000378:metabolism; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C482527:FNBP1L protein, human; D011108:Polymers; D014157:Transcription Factors; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C058483:virG protein, Shigella flexneri