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KMID : 0620920190510070085
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Experimental & Molecular Medicine
2019 Volume.51 No. 7 p.85 ~ p.85
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SPIN90, an adaptor protein, alters the proximity between Rab5 and Gapex5 and facilitates Rab5 activation during EGF endocytosis
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Kim Hwan
Oh Hye-Jin
Oh Young-Soo
Bae Jeom-Il
Hong Nan-Hyung
Park Su-Jung
Ahn Su-Yeon
Lee Miriam
Rhee Sang-Myung
Lee Sung-Haeng
Jun Young-Soo
Kim Sung-Hyun
Huh Yun-Hyun
Song Woo-Keun
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Abstract
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During ligand-mediated receptor endocytosis, the small GTPase Rab5 functions in vesicle fusion and trafficking. Rab5 activation is known to require interactions with its guanine nucleotide-exchange factors (GEFs); however, the mechanism regulating Rab5 interactions with GEFs remains unclear. Here, we show that the SH3-adapter protein SPIN90 participates in the activation of Rab5 through the recruitment of both Rab5 and its GEF, Gapex5, to endosomal membranes during epidermal growth factor (EGF)-mediated endocytosis. SPIN90 strongly interacts with the inactive Rab5/GDI2 complex through its C-terminus. In response to EGF signaling, extracellular signal-regulated kinase (ERK)-mediated phosphorylation of SPIN90 at Thr-242 enables SPIN90 to bind Gapex5 through its N-terminal SH3 domain. Gapex5 is a determinant of Rab5 membrane targeting, while SPIN90 mediates the interaction between Gapex5 and Rab5 in a phosphorylation-dependent manner. Collectively, our findings suggest that SPIN90, as an adaptor protein, simultaneously binds inactive Rab5 and Gapex5, thereby altering their spatial proximity and facilitating Rab5 activation.
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KEYWORD
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Endocytosis, Growth factor signalling, Small GTPases
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