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[PMID]: | 28073834 |
[Au] Autor: | Kim HJ; Kwon S; Nam SH; Jung JW; Kang M; Ryu J; Kim JE; Cheong JG; Cho CY; Kim S; Song DG; Kim YN; Kim TY; Jung MK; Lee KM; Pack CG; Lee JW |
[Ad] Endereço: | Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea. |
[Ti] Título: | Dynamic and coordinated single-molecular interactions at TM4SF5-enriched microdomains guide invasive behaviors in 2- and 3-dimensional environments. |
[So] Source: | FASEB J;31(4):1461-1481, 2017 Apr. | [Is] ISSN: | 1530-6860 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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 (T ERMs) on the directionality of cell migration. Physical association of TM4SF5 with epidermal growth factor receptor (EGFR) and integrin α5 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 the migrating leading region more than at the rear, TM4SF5 and integrin α5 colocalized evenly throughout cells. Cholesterol depletion and disruption in TM4SF5 post-translational modifications, including -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 α5 activity. Altogether, we showed that TM4SF5 dynamically interacted with EGFR and integrin α5 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. |
[Mh] Termos MeSH primário: |
Microdomínios da Membrana/metabolismo Proteínas de Membrana/metabolismo
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[Mh] Termos MeSH secundário: |
Linhagem Celular Tumoral Movimento Celular Colesterol/metabolismo Glicosilação Células HEK293 Hepatócitos/metabolismo Hepatócitos/fisiologia Hepatócitos/ultraestrutura Seres Humanos Integrina alfa5/metabolismo Lipoilação Microdomínios da Membrana/ultraestrutura Ligação Proteica Processamento de Proteína Pós-Traducional Receptor do Fator de Crescimento Epidérmico/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Integrin alpha5); 0 (Membrane Proteins); 0 (TM4SF5 protein, human); 97C5T2UQ7J (Cholesterol); EC 2.7.10.1 (Receptor, Epidermal Growth Factor) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 170906 |
[Lr] Data última revisão:
| 170906 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170112 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1096/fj.201600944RR |
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