CHLAMYDIA TRACHOMATIS PHOSPHORYLATES AKT SUBSTRATE 160 TO CAPTURE HOST SPHINGOLIPIDS

CAPMANY A; GAMBARTE J; DAMIANI MT

Rosario, Santa Fe

Congreso; L Reunión SAIB 2014; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Chlamydia trachomatis, an obligate intracellular bacterium, replicates in a vacuole called inclusion, where intercepts certain Rab-mediated transport pathways to capture nutrients from host cells. Rab proteins, the master controllers of intracellular trafficking, are GTPases that switch between inactive GDP-bound and active GTP-bound forms. This cycling is modulated by GTP Activating Proteins (GAPs) and GDP Exchange Factors (GEFs) that respectively, promote the GTP hydrolysis, or the replacement of GDP by GTP. We demonstrated that Rab14 is specifically recruited to the inclusion and promotes the delivery of host Golgi-synthesized sphingolipids to the inclusion. Our findings suggest that C. trachomatis, through Akt phosphorylation, might inactivate AS160, a GAP of Rab14, to favour Rab14 GTP-bound state and thereby the arrival of sphingolipids to the inclusion. Our results reveal that both enzymes, Akt and AS160, present two waves of phosphorylation in infected cells. The first one is around 30 minute post-infection (pi) and the second one occurs at mid-stage of chlamydial lifecycle between 8-12 hours pi. Specific Akt inhibitors (iAkt) impair AS160 phosphorylation, and consequently, bacterial growth. C. trachomatis usurps Akt pathway to inactivate AS160, thus promoting Rab14-mediated sphingolipid transport to the inclusion.