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Dynamic and coordinated single‐molecular interactions at TM4SF5‐enriched microdomains guide invasive behaviors in 2‐ and 3‐dimensional environments
Author(s) -
Kim HyeJin,
Kwon Sojung,
Nam Seo Hee,
Jung Jae Woo,
Kang Minkyung,
Ryu Jihye,
Kim Ji Eon,
Cheong JinGyu,
Cho Chang Yun,
Kim Somi,
Song DaeGeun,
Kim YongNyun,
Kim Tai Young,
Jung MinKyo,
Lee KyungMin,
Pack ChanGi,
Lee Jung Weon
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600944rr
Subject(s) - tetraspanin , integrin , microbiology and biotechnology , biology , cell migration , lipid raft , extracellular matrix , directionality , receptor , motility , signal transduction , cell , genetics
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 5 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 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 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. FASEB J . 31, 1461–1481 (2017) www.fasebj.org