Dynamic and coordinated single-molecular interactions at TM4SF5-enriched microdomains guide invasive behaviors in 2-and 3-dimensional environments
Dynamic and coordinated single-molecular interactions at TM4SF5-enriched microdomains guide invasive behaviors in 2-and 3-dimensional environments
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DOI：
10.1096/fj.201600944rr
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发表时间：
2017-04-01
期刊：
影响因子：
4.8
通讯作者：
Lee, Jung Weon
中科院分区：
文献类型：
--
作者：
Kim, Hye-Jin;Kwon, Sojung;Lee, Jung Weon
膜蛋白感知细胞外信号并调节细胞内信号以协调细胞迁移过程中的方向性和速度。它们通常定位于特定区域，如脂筏或四跨膜蛋白富集的微区;然而，四跨膜蛋白与细胞表面四跨膜蛋白富集的微区内的不同受体的动态相互作用在很大程度上仍未被探索。在这里，我们研究了tetraspan（in）TM 4SF 5（跨膜4 L 6家族成员5）富集微区（T5 ERMs）对细胞迁移方向性的影响。通过实时荧光互相关光谱和更高分辨率显微镜观察迁移细胞前沿的TM 4SF 5与表皮生长因子受体（EGFR）和整合素α 5的物理联系，推测形成了富含TM 4SF 5的微区。而TM 4SF 5和EGFR共定位在迁移的前导区多于后部，TM 4SF 5和整合素a5在整个细胞中均匀共定位。胆固醇消耗和TM 4SF 5翻译后修饰（包括N-糖基化和棕榈酰化）的破坏，改变了TM 4SF 5相互作用和细胞定位，导致细胞迁移速度和方向性在二维或三维条件下降低。TM 4SF 5控制定向细胞迁移和侵袭，重要的是，这些TM 4SF 5功能依赖于胆固醇、TM 4SF 5翻译后修饰以及EGFR和整合素α 5活性。总之，我们表明TM 4SF 5在迁移细胞中与EGFR和整合素α 5动态相互作用，以控制方向性和侵袭性。金，H.- J.，Kwon，S.，南，S。H、Jung，J.W.，Kang，M.，Ryu，J.，金，J.E.，张志成G.，乔角，澳-地是的，Kim，S.，宋，D.- G.，金，Y.- N.，金，T。是的，Jung，M. K.，李，K.- M.，帕克，C.- G.，Lee，J.W. TM 4SF 5富集微区的动态和协调的单分子相互作用指导2维和3维环境中的侵入行为。FASEB J. 31，1461-1481（2017）。www.fasebj.org
Membrane proteins sense extracellular cues and transduce intracellular signaling to coordinate directionality and speed during cellular migration. They are often localized to specific regions, as with lipid rafts or tetraspanin-enriched microdomains; however, the dynamic interactions of tetraspanins with diverse receptors within tetraspanin-enriched microdomains on cellular surfaces remain largely unexplored. Here, we investigated effects of tetraspan(in) TM4SF5 (transmembrane 4 L6 family member 5)-enriched microdomains (T5ERMs) on the directionality of cell migration. Physical association of TM4SF5 with epidermal growth factor receptor (EGFR) and integrin alpha 5 was visualized by live fluorescence cross-correlation spectroscopy and higher-resolution microscopy at the leading edge of migratory cells, presumably forming TM4SF5-enriched microdomains. Whereas TM4SF5 and EGFR colocalized at themigrating leading region more than at the rear, TM4SF5 and integrin a5 colocalized evenly throughout cells. Cholesterol depletion and disruption in TM4SF5 post-translational modifications, including N-glycosylation and palmitoylation, altered TM4SF5 interactions and cellular localization, which led to less cellular migration speed and directionality in 2-or 3-dimensional conditions. TM4SF5 controlled directional cell migration and invasion, and importantly, these TM4SF5 functions were dependent on cholesterol, TM4SF5 post-translational modifications, and EGFR and integrin alpha 5 activity. Altogether, we showed that TM4SF5 dynamically interacted with EGFR and integrin a5 in migratory cells to control directionality and invasion.-Kim, H.-J., Kwon, S., Nam, S. H., Jung, J. W., Kang, M., Ryu, J., Kim, J. E., Cheong, J.-G., Cho, C. Y., Kim, S., Song, D.-G., Kim, Y.-N., Kim, T. Y., Jung, M.-K., Lee, K.-M., Pack, C.-G., Lee, J. W. Dynamic and coordinated single-molecular interactions at TM4SF5-enriched microdomains guide invasive behaviors in 2-and 3-dimensional environments. FASEB J. 31, 1461-1481 (2017). www.fasebj.org