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Category: Bacterial Pathogenesis
Cell Biology of the Chlamydial Inclusion, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555817329/9781555816742_Chap08-1.gif /docserver/preview/fulltext/10.1128/9781555817329/9781555816742_Chap08-2.gifAbstract:
All aspects of Chlamydia survival are intimately linked to the cell biology of its host. Recent advances in cell biological techniques and new tools to perform loss-of-function experiments in mammalian cells have accelerated one's understanding of the extent to which Chlamydia manipulates the host. Homotypic fusion of C. trachomatis inclusions could serve to consolidate resources and reduce competition among multiple growing inclusions. It is clear that Incs on early inclusions likely play important roles in remodeling the nascent inclusion to segregate from the endolysosomal pathway and maintain single inclusion morphology in fusogenic Chlamydia species. However, the role played by soluble effectors secreted early or even during entry should not be discounted when considering early interactions with host cell biology. Of host sphingolipids (SLs), only sphingomyelin, and not glucosylceramide, is delivered to the chlamydial inclusion , suggesting highly specific interactions with host pathways. Multivesicular bodies (MVBs) are late endocytic compartments in which the limiting membrane of endosomes has invaginated into the lumen to form intraluminal vesicles containing membrane proteins destined for degradation. Much of the focus of investigations into chlamydial anti-immune strategies has centered on the interruption of innate immune signaling pathways. Given the long evolutionary history of the association of Chlamydia spp. with eukaryotic cells, these bacteria are expected to reveal new insights into basic aspects of eukaryotic cell biology, primordial mechanisms of cell autonomous innate immunity, and novel pathogenic strategies.
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Early events in nascent inclusion biogenesis. Soon after chlamydial entry, the nascent inclusion rapidly loses plasma membrane and early endocytic and classic endolysosomal markers ( Scidmore et al., 2003 ), including the phosphoinositides PI(4,5)P2 and PI3P and endolysosomal Rabs (Rab5, Rab7, and Rab9) ( Moorhead et al., 2010 ; Rzomp et al., 2003 ). Recycling endosomes and their associated Rabs localize to early inclusions ( Rzomp et al., 2006 , 2003 ) and may facilitate migration to the MTOC, in a microtubule- and dynein-dependent manner ( Clausen et al., 1997 ). p150(Glued), the component of the dynactin protein complex linking vesicular cargo to dynein, is required for migration to the MTOC, although p50 dynamitin is not ( Grieshaber et al., 2003 ). Chlamydia inclusion membrane proteins IncB and Ct850 are postulated to play a role in this interaction to promote association of the nascent inclusion with the microtubule-organizing center ( Mital et al., 2010 ). Endocytic pathway-associated SNAREs, including Vamp3, -7, and -8, localize around the inclusion in a fusion-inhibited state potentially as a result of interactions with Chlamydia Incs (IncA, CT813, and CT223) ( Delevoye et al., 2008 ; Paumet et al., 2009 ). These Inc proteins have been proposed to function as inhibitory SNARE (iSNARE) mimics ( Paumet et al., 2009 ). doi:10.1128/9781555817329.ch8.f1
Early events in nascent inclusion biogenesis. Soon after chlamydial entry, the nascent inclusion rapidly loses plasma membrane and early endocytic and classic endolysosomal markers ( Scidmore et al., 2003 ), including the phosphoinositides PI(4,5)P2 and PI3P and endolysosomal Rabs (Rab5, Rab7, and Rab9) ( Moorhead et al., 2010 ; Rzomp et al., 2003 ). Recycling endosomes and their associated Rabs localize to early inclusions ( Rzomp et al., 2006 , 2003 ) and may facilitate migration to the MTOC, in a microtubule- and dynein-dependent manner ( Clausen et al., 1997 ). p150(Glued), the component of the dynactin protein complex linking vesicular cargo to dynein, is required for migration to the MTOC, although p50 dynamitin is not ( Grieshaber et al., 2003 ). Chlamydia inclusion membrane proteins IncB and Ct850 are postulated to play a role in this interaction to promote association of the nascent inclusion with the microtubule-organizing center ( Mital et al., 2010 ). Endocytic pathway-associated SNAREs, including Vamp3, -7, and -8, localize around the inclusion in a fusion-inhibited state potentially as a result of interactions with Chlamydia Incs (IncA, CT813, and CT223) ( Delevoye et al., 2008 ; Paumet et al., 2009 ). These Inc proteins have been proposed to function as inhibitory SNARE (iSNARE) mimics ( Paumet et al., 2009 ). doi:10.1128/9781555817329.ch8.f1
The inclusion interacts with multiple subcellular compartments. Fragmented Golgi apparatus ministacks, the ER, LDs, mitochondria, and recycling endosomes (RE) closely associate with the inclusion ( Heuer et al., 2009 ; Peterson and de la Maza, 1988 ; Kumar et al., 2006 ; Matsumoto et al., 1991 ; van Ooij et al., 1997 ; Scidmore et al., 1996 ). These interactions may facilitate nutrient acquisition directly from these organelles. Golgi apparatus fragmentation enhances sphingolipid uptake ( Heuer et al., 2009 ), and lipid droplets translocate into the lumen of the inclusion ( Cocchiaro et al., 2008 ). Additional pathways for lipid delivery (inset) include vesicular transport of Golgi apparatus-derived exocytic vesicles ( Hackstadt et al., 1996 ; Carabeo et al., 2003 ), MVBs ( Beatty, 2008 , 2006 ), and transfer at membrane contact sites (MCS) between the ER and inclusion membranes ( Derré et al., 2011 ; Elwell et al., 2011 ). The inclusion remains in close association with centrosomes at the MTOC throughout intracellular infection ( Grieshaber et al., 2006 ). doi:10.1128/9781555817329.ch8.f2
The inclusion interacts with multiple subcellular compartments. Fragmented Golgi apparatus ministacks, the ER, LDs, mitochondria, and recycling endosomes (RE) closely associate with the inclusion ( Heuer et al., 2009 ; Peterson and de la Maza, 1988 ; Kumar et al., 2006 ; Matsumoto et al., 1991 ; van Ooij et al., 1997 ; Scidmore et al., 1996 ). These interactions may facilitate nutrient acquisition directly from these organelles. Golgi apparatus fragmentation enhances sphingolipid uptake ( Heuer et al., 2009 ), and lipid droplets translocate into the lumen of the inclusion ( Cocchiaro et al., 2008 ). Additional pathways for lipid delivery (inset) include vesicular transport of Golgi apparatus-derived exocytic vesicles ( Hackstadt et al., 1996 ; Carabeo et al., 2003 ), MVBs ( Beatty, 2008 , 2006 ), and transfer at membrane contact sites (MCS) between the ER and inclusion membranes ( Derré et al., 2011 ; Elwell et al., 2011 ). The inclusion remains in close association with centrosomes at the MTOC throughout intracellular infection ( Grieshaber et al., 2006 ). doi:10.1128/9781555817329.ch8.f2