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WAFL, a new protein involved in regulation of early endocytic transport at the intersection of actin and microtubule dynamics |
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| Authors: | Ing-Marie Viklund Pontus Aspenström Vannary Meas-Yedid Jolanta Kopec Daniel Ågren Gunter Schneider Mauro D'Amato Jean-Christophe Olivo-Marin Guy Tran Van Nhieu Sven Pettersson |
| Institution: | a Strategic Research Center IRIS, Karolinska Institute, Stockholm, Sweden b Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden c Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Uppsala, Sweden d Unité Analyse d'Images Quantitative, Institut Pasteur, Paris, France e Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. f Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France g Genome Institute of Singapore, Singapore |
| Abstract: | We have previously identified a new gene with sequence homology to the WASP-family of actin regulators denoted WAFL (WASP and FKBP-like). Here we report a possible biological function for WAFL, by demonstrating an association to early endosomes via its central coiled-coil domain. Further we show by functional and structural studies that WAFL is associated with both microtubules and the actin filament system, the two means of transport of early endosomes. In addition, WAFL interacts with WASP-interacting protein (WIP) and actin, thus linking WAFL to actin dynamics. The use of RNAi depletion of WAFL shows that WAFL-deficient cells display delayed transport of endosomal cargo. Our findings are compatible with a model whereby WAFL is involved in the transport of early endosomes at the level of transition between microfilament-based and microtubule-based movement. |
| Keywords: | WAFL WASP and FKBP-like WASP Wiskott-Aldrich syndrome protein FKPB FK506-binding protein WIP WASP-interacting protein IBD inflammatory bowel disease UC ulcerative colitis CD Crohn's disease |
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