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
- 송대근; 김혜진; 권소정; 남서희; 정재우; 강민경; 류지혜; 김지언; 정진규; 조창연; 김소미; Yong-Nyun Kim; 김태영; Min-Kyo Jung; 이경민; Chan-Gi Pack; 이정원
- 3D cell culture; FCCS; migration; protein interaction affinity; membrane proteins
- Issue Date
- The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- VOL 31, NO 4-1481
- 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 a5 was visualized by live fluorescence cross-correlation spectroscopy and higher-resolutionmicroscopy 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, alteredTM4SF5 interactions and cellular localization,which led to less cellular migration speed and directionality in 2- or 3-dimensional conditions. TM4SF5 controlled directional cellmigration and invasion, and importantly, these TM4SF5 functionswere dependent on cholesterol, TM4SF5 post-translational modifications, and EGFRand integrina5 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- an
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