scholarly journals SARS‐CoV‐2 spike protein harnesses SNX27‐mediated endocytic recycling pathway

MedComm ◽  
2021 ◽  
Author(s):  
Lin Zhao ◽  
Kunhong Zhong ◽  
Jia Zhao ◽  
Xin Yong ◽  
Aiping Tong ◽  
...  

2014 ◽  
Vol 1843 (12) ◽  
pp. 2991-3003 ◽  
Author(s):  
María Gabriela Márquez ◽  
Yamila Romina Brandán ◽  
Edith del Valle Guaytima ◽  
Carlos Humberto Paván ◽  
Nicolás Octavio Favale ◽  
...  


mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Michael G. Connor ◽  
Amanda R. Pulsifer ◽  
Donghoon Chung ◽  
Eric C. Rouchka ◽  
Brian K. Ceresa ◽  
...  

ABSTRACTYersinia pestishas evolved many strategies to evade the innate immune system. One of these strategies is the ability to survive within macrophages. Upon phagocytosis,Y. pestisprevents phagolysosome maturation and establishes a modified compartment termed theYersinia-containing vacuole (YCV).Y. pestisactively inhibits the acidification of this compartment, and eventually, the YCV transitions from a tight-fitting vacuole into a spacious replicative vacuole. The mechanisms to generate the YCV have not been defined. However, we hypothesized that YCV biogenesis requiresY. pestisinteractions with specific host factors to subvert normal vesicular trafficking. In order to identify these factors, we performed a genome-wide RNA interference (RNAi) screen to identify host factors required forY. pestissurvival in macrophages. This screen revealed that 71 host proteins are required for intracellular survival ofY. pestis. Of particular interest was the enrichment for genes involved in endosome recycling. Moreover, we demonstrated thatY. pestisactively recruits Rab4a and Rab11b to the YCV in a type three secretion system-independent manner, indicating remodeling of the YCV byY. pestisto resemble a recycling endosome. While recruitment of Rab4a was necessary to inhibit YCV acidification and lysosomal fusion early during infection, Rab11b appeared to contribute to later stages of YCV biogenesis. We also discovered thatY. pestisdisrupts global host endocytic recycling in macrophages, possibly through sequestration of Rab11b, and this process is required for bacterial replication. These data provide the first evidence thatY. pestistargets the host endocytic recycling pathway to avoid phagolysosomal maturation and generate the YCV.IMPORTANCEYersinia pestiscan infect and survive within macrophages. However, the mechanisms that the bacterium use to subvert killing by these phagocytes have not been defined. To provide a better understanding of these mechanisms, we used an RNAi approach to identify host factors required for intracellularY. pestissurvival. This approach revealed that the host endocytic recycling pathway is essential forY. pestisto avoid clearance by the macrophage. We further demonstrate thatY. pestisremodels the phagosome to resemble a recycling endosome, allowing the bacterium to avoid the normal phagolysosomal maturation pathway. Moreover, we show that infection withY. pestisdisrupts normal recycling in the macrophage and that disruption is required for bacterial replication. These findings provide the first evidence thatY. pestistargets the host endocytic recycling pathway in order to evade killing by macrophages.



2009 ◽  
Vol 10 (1) ◽  
pp. 84 ◽  
Author(s):  
Byung Chung ◽  
Srikumar M Raja ◽  
Robert J Clubb ◽  
Chun Tu ◽  
Manju George ◽  
...  


PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e96760 ◽  
Author(s):  
Ballington L. Kinlock ◽  
Yudi Wang ◽  
Tiffany M. Turner ◽  
Chenliang Wang ◽  
Bindong Liu


Traffic ◽  
2008 ◽  
Vol 9 (9) ◽  
pp. 1446-1457 ◽  
Author(s):  
Duarte C Barral ◽  
Marco Cavallari ◽  
Peter J McCormick ◽  
Salil Garg ◽  
Anthony I Magee ◽  
...  


2004 ◽  
Vol 17 (1) ◽  
pp. 164-181 ◽  
Author(s):  
Sophie Haupt ◽  
Graham H. Cowan ◽  
Angelika Ziegler ◽  
Alison G. Roberts ◽  
Karl J. Oparka ◽  
...  


2006 ◽  
Vol 17 (2) ◽  
pp. 598-606 ◽  
Author(s):  
David Padrón ◽  
Renee D. Tall ◽  
Michael G. Roth

RNA interference-mediated depletion of phospholipase D2 (PLD2), but not PLD1, inhibited recycling of transferrin receptors in HeLa cells, whereas the internalization rate was unaffected by depletion of either PLD. Although reduction of both PLD isoforms inhibits PLD activity stimulated by phorbol 12-myristic 13-acetate, only depletion of PLD2 decreased nonstimulated activity. Cells with reduced PLD2 accumulated a greater fraction of transferrin receptors in a perinuclear compartment that was positive for Rab11, a marker of recycling endosomes. EFA6, an exchange factor for Arf6, has been proposed to stimulate the recycling of transferrin receptors. Thus, one consequence of EFA6 overexpression would be a reduction of the internal pool of receptors. We confirmed this observation in control HeLa cells; however, overexpression of EFA6 failed to decrease the internal pool of transferrin receptors that accumulate in cells previously depleted of PLD2. These observations suggest that either PLD2 is required for a constitutive Arf6-mediated recycling pathway or in the absence of PLD2 transferrin receptors accumulate in recycling endosomes that are not responsive to overexpression of EFA6.



2015 ◽  
Vol 209 (1) ◽  
pp. 97-110 ◽  
Author(s):  
FoSheng Hsu ◽  
Fenghua Hu ◽  
Yuxin Mao

It is well established that the spatial- and temporal-restricted generation and turnover of phosphoinositides (PIs) by a cascade of PI-metabolizing enzymes is a key regulatory mechanism in the endocytic pathway. Here, we demonstrate that the Sac1 domain–containing protein Sac2 is a PI 4-phosphatase that specifically hydrolyzes phosphatidylinositol 4-phosphate in vitro. We further show that Sac2 colocalizes with early endosomal markers and is recruited to transferrin (Tfn)-containing vesicles during endocytic recycling. Exogenous expression of the catalytically inactive mutant Sac2C458S resulted in altered cellular distribution of Tfn receptors and delayed Tfn recycling. Furthermore, genomic ablation of Sac2 caused a similar perturbation on Tfn and integrin recycling as well as defects in cell migration. Structural characterization of Sac2 revealed a unique pleckstrin-like homology Sac2 domain conserved in all Sac2 orthologues. Collectively, our findings provide evidence for the tight regulation of PIs by Sac2 in the endocytic recycling pathway.



2018 ◽  
Vol 218 (suppl_5) ◽  
pp. S388-S396 ◽  
Author(s):  
Asuka Nanbo ◽  
Yusuke Ohba


2017 ◽  
Vol 292 (14) ◽  
pp. 5737-5747 ◽  
Author(s):  
Kristin Dauner ◽  
Walaa Eid ◽  
Riya Raghupathy ◽  
John F. Presley ◽  
Xiaohui Zha


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