Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain.
Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain.
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DOI：
10.1016/j.devcel.2017.10.024
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发表时间：
2017-11-20
影响因子：
11.8
通讯作者：
Sherwood DR
中科院分区：
文献类型：
--
作者：
Naegeli KM;Hastie E;Garde A;Wang Z;Keeley DP;Gordon KL;Pani AM;Kelley LC;Morrissey MA;Chi Q;Goldstein B;Sherwood DR
侵袭性细胞使用小的侵袭伪足来破坏基底膜（BM），基底膜是包裹组织的致密基质。破裂后，形成一个大的突起，通过不太清楚的机制为组织进入清除路径。使用RNAi筛选C.在线虫锚细胞（AC）侵入的过程中，我们发现BM突破位点的NTA-6（netrin）/NTA-40（DCC）信号传导使用外泌囊和SNARE SNAP-29指导溶酶体的胞吐作用，以形成侵入外阴组织的大突起。活细胞成像显示，突出物富含基质金属蛋白酶ZMP-1，并瞬时扩大AC体积超过20%，取代周围BM和外阴上皮。光漂白和遗传扰动表明，BM受体肌营养不良蛋白聚糖在突出物的颈部形成膜扩散屏障，使突出物生长。这些研究共同定义了一种netrin依赖性途径，该途径构建了一种侵入性突起，一种专门用于突破组织屏障的分离的溶酶体衍生的膜结构。在基底膜破裂后，侵袭性细胞如何清除进入通道？Naegeli等在C.由netrin介导的途径调节的定向溶酶体胞吐作用的秀丽线虫在侵入伪足后形成大的侵入性突起。通过肌营养不良蛋白聚糖膜扩散屏障隔离，突起扩展以产生组织开口。
Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in C. elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume more than 20%, displacing surrounding BM and vulval epithelium. Photobleaching and genetic perturbations showed that the BM receptor dystroglycan forms a membrane diffusion barrier at the neck of the protrusion that enables protrusion growth. Together these studies define a netrin dependent pathway that builds an invasive protrusion, an isolated lysosome-derived membrane structure specialized to breach tissue barriers. How do invasive cells clear an entry path after basement membrane breach? Naegeli et al. show in C. elegans that directed lysosome exocytosis regulated by a netrin-mediated pathway builds the large invasive protrusion formed after invadopodia. Isolated by a dystroglycan membrane diffusion barrier, the protrusion expands to create tissue openings.
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影响因子：
4
作者：
Gawden-Bone, Christian;Zhou, Zhongjun;Lucocq, John
通讯作者：
Lucocq, John
影响因子：
4.6
作者：
Armenti, Stephen T.;Lohmer, Lauren L.;Nance, Jeremy
通讯作者：
Nance, Jeremy
DOI：
10.1083/jcb.201312098
发表时间：
2014-03-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hagedorn EJ;Kelley LC;Naegeli KM;Wang Z;Chi Q;Sherwood DR
通讯作者：
Sherwood DR
影响因子：
11.8
作者：
Hagedorn, Elliott J.;Yashiro, Hanako;Ziel, Joshua W.;Ihara, Shinji;Wang, Zheng;Sherwood, David R.
通讯作者：
Sherwood, David R.
影响因子：
4.6
作者：
Johnson, RP;Kang, SH;Kramer, JM
通讯作者：
Kramer, JM