Internalization of the Active Subunit of the Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Is Dependent upon Cellugyrin (Synaptogyrin 2), a Host Cell Non-Neuronal Paralog of the Synaptic Vesicle Protein, Synaptogyrin 1.
Internalization of the Active Subunit of the Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Is Dependent upon Cellugyrin (Synaptogyrin 2), a Host Cell Non-Neuronal Paralog of the Synaptic Vesicle Protein, Synaptogyrin 1.
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DOI：
10.3389/fcimb.2017.00469
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发表时间：
2017
影响因子：
5.7
通讯作者：
Shenker BJ
中科院分区：
文献类型：
--
作者：
Boesze-Battaglia K;Walker LP;Dhingra A;Kandror K;Tang HY;Shenker BJ
The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is a heterotrimeric AB2 toxin capable of inducing lymphocytes, and other cell types, to undergo cell cycle arrest and apoptosis. Exposure to Cdt results in binding to the cell surface followed by internalization and translocation of the active subunit, CdtB, to intracellular compartments. These events are dependent upon toxin binding to cholesterol in the context of lipid rich membrane microdomains often referred to as lipid rafts. We now demonstrate that, in addition to binding to the plasma membrane of lymphocytes, another early and critical event initiated by Cdt is the translocation of the host cell protein, cellugyrin (synaptogyrin-2) to the same cholesterol-rich microdomains. Furthermore, we demonstrate that cellugyrin is an intracellular binding partner for CdtB as demonstrated by immunoprecipitation. Using CRISPR/cas9 gene editing we established a Jurkat cell line deficient in cellugyrin expression (JurkatCg−); these cells were capable of binding Cdt, but unable to internalize CdtB. Furthermore, JurkatCg− cells were not susceptible to Cdt-induced toxicity; these cells failed to exhibit blockade of the PI-3K signaling pathway, cell cycle arrest or cell death. We propose that cellugyrin plays a critical role in the internalization and translocation of CdtB to critical intracellular target sites. These studies provide critical new insight into the mechanism by which Cdt, and in particular, CdtB is able to induce toxicity.
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影响因子：
6.7
作者：
Eshraghi A;Dixon SD;Tamilselvam B;Kim EJ;Gargi A;Kulik JC;Damoiseaux R;Blanke SR;Bradley KA
通讯作者：
Bradley KA
影响因子：
6.7
作者：
Bielaszewska M;Rüter C;Bauwens A;Greune L;Jarosch KA;Steil D;Zhang W;He X;Lloubes R;Fruth A;Kim KS;Schmidt MA;Dobrindt U;Mellmann A;Karch H
通讯作者：
Karch H
DOI：
10.1016/j.bbamcr.2008.11.017
发表时间：
2009-03-01
影响因子：
5.1
作者：
Guerra, Lina;Nemec, Kathleen N.;Teter, Ken
通讯作者：
Teter, Ken
影响因子：
5.7
作者：
Boesze-Battaglia K;Alexander D;Dlakić M;Shenker BJ
通讯作者：
Shenker BJ
影响因子：
3.1
作者：
Cortes-Bratti, X;Chaves-Olarte, E;Thelestam, M
通讯作者：
Thelestam, M