Filopodia are thin, actin-based membrane protrusions with roles in sensing external mechanical and chemical cues, such as growth factor gradients in tissues. It was proposed that the chemical sensing role of filopodia is achieved through clearance of activated signaling receptors from filopodia. Type I insulin-like growth factor receptor (IGF1R) is a key regulator of normal development and growth, as well as tumor development and progression. Its biological roles depend on its activation upon IGF1 binding at the cell membrane. IGF1R behavior at the cell membrane and in particular in filopodia, has not been established. We found that IGF1 activation led to a gradual reduction in IGF1R puncta in filopodia, and that this clearance depended on actin, non-muscle myosin II, and IGF1R kinase activity. Using single particle tracking of filopodial IGF1R, we established that ligand-free IGF1R undergoes non-directional unidimensional diffusion along the filopodium. Moreover, after initial diffusion, the ligand-bound IGF1R is actively transported along the filopodium towards the filopodium base, and consequently cleared from the filopodium. Our results show that IGF1R can move directionally on the plasma membrane protrusions, supporting a sensory role for filopodia in interpreting local IGF1 gradients.
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Cover Image
Cover Image
In this issue Qu and colleagues (pp. 3649–3660) have determined the crystal structure of TauA and have characterized its thermodynamic binding parameters by isothermal titration calorimetry in complex with taurine and different alkanesulfonates. The cover figure shows desolvation of the taurine binding protein TauA dictates ligand selectivity. TauA is shown in cartoon with taurine in red sticks. Water droplets indicate fully hydrated binding site. Image provided by Konstantinos Beis.
IGF1R undergoes active and directed centripetal transport on filopodia upon receptor activation
Denis Krndija, Michael Fairhead; IGF1R undergoes active and directed centripetal transport on filopodia upon receptor activation. Biochem J 12 December 2019; 476 (23): 3583–3593. doi: https://doi.org/10.1042/BCJ20190665
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