The late endocytic Rab39a GTPase regulates multivesicular bodies-chlamydial inclusion interaction and bacterial growth

Abstract

Given their obligate intracellular lifestyle, Chlamydia trachomatis ensure that they have access to multiple host sources of essential lipids by interfering with vesicular transport. These bacteria hijack Rab6-, Rab11-and Rab14-controlled trafficking pathways to acquire sphingomyelin from the Golgi complex. Another important source of sphingolipids, phospholipids and cholesterol are multivesicular bodies (MVBs). Despite their participation in chlamydial inclusion development and bacterial replication, the molecular mechanisms mediating the interaction between MVBs and chlamydial inclusions remain unknown. In the present study, we demonstrate that Rab39a labels a subset of late endocytic vesicles -mainly MVBs -that move along microtubules. Moreover, Rab39a is actively recruited to chlamydial inclusions throughout the pathogen life cycle by a bacterial-driven process that depends on the Rab39a GTP-or GDP-binding state. Interestingly, Rab39a participates in the delivery of MVBs and host sphingolipids to maturing chlamydial inclusions, thereby promoting inclusion growth and bacterial development. Taken together, our findings indicate that Rab39a favours chlamydial replication and infectivity. This is the first report showing that a late endocytic Rab GTPase is involved in chlamydial infection development.

Chlamydia cell biology and pathogenesis

“…RAB4 and RAB11 mediate the interactions of the inclusion with the transferrin slow-recycling pathway to acquire iron 7 and may also contribute to transport along microtubules 53 . RAB6, RAB11 and RAB14 facilitate lipid acquisition from the Golgi apparatus 53 , whereas RAB39 participates in the delivery of lipids from multivesicular bodies 54 . The recruitment of RAB proteins is probably driven by species-specific Inc–RAB interactions.…”

“…Sphingomyelin and cholesterol are acquired from the Golgi apparatus and multivesicular bodies 7 . Host proteins that are implicated in this vesicle-dependent acquisition include ARF GTPases 57,72,73 , the ARF guanine nucleotide exchange factor GBF1 (REFS 72,73), RAB GTPases (specifically, RAB6, RAB11, RAB14 and RAB39) 53,54 , RAB11FIP2 (REF. 55), VAMP4 (REF.…”

Rab GTPase Mediating Regulation of NALP3 in Colorectal Cancer

“…Approximately 70 different Rab proteins have been identified in humans that are associated with a specific transport event [ 26 ]. Among these proteins, Rab39a, which is involved in late endocytosis [ 27 , 28 ], contains highly conserved caspase-1 cleavage sites, and the overexpression of Rab39a could result in increased IL-1β secretion [ 29 ]. Additionally, Rab8, which contributes to exocytosis regulation, has also been shown to facilitate IL-1β secretion [ 30 , 31 ].…”

Diverted recycling—Shigella subversion of Rabs

“…52,53 It also recruits Rab39, which is involved in multi-vesicular bodies (MVBs) trafficking, for inclusion growth and bacterial development. 54 The specific bacterial effectors responsible of such subversions are still unknown. Finally, Yersinia pestis promotes the recruitment of Rab1 to the BCVs.…”