Role for the IFT-A Complex in Selective Transport to the Primary Cilium
Intraflagellar transport sub-complex A (IFT-A) is known to regulate retrograde IFT in the cilium. To rigorously assess its other possible roles, we knocked out an IFT-A subunit, IFT121/WDR35, in mammalian cells and screened the localization of more than 50 proteins. We found that Wdr35 regulates cil...
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doaj-cc98e842bd024865b222b723411c82682020-11-25T01:52:00ZengElsevierCell Reports2211-12472016-11-011761505151710.1016/j.celrep.2016.10.018Role for the IFT-A Complex in Selective Transport to the Primary CiliumWenxiang Fu0Lei Wang1Sehyun Kim2Ji Li3Brian David Dynlacht4Department of Pathology and Perlmutter Cancer Center, NYU School of Medicine, Smilow Research Building, 522 First Avenue, New York, NY 10016, USADepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, Smilow Research Building, 522 First Avenue, New York, NY 10016, USADepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, Smilow Research Building, 522 First Avenue, New York, NY 10016, USADepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USADepartment of Pathology and Perlmutter Cancer Center, NYU School of Medicine, Smilow Research Building, 522 First Avenue, New York, NY 10016, USAIntraflagellar transport sub-complex A (IFT-A) is known to regulate retrograde IFT in the cilium. To rigorously assess its other possible roles, we knocked out an IFT-A subunit, IFT121/WDR35, in mammalian cells and screened the localization of more than 50 proteins. We found that Wdr35 regulates cilium assembly by selectively regulating transport of distinct cargoes. Beyond its role in retrograde transport, we show that Wdr35 functions in fusion of Rab8 vesicles at the nascent cilium, protein exit from the cilium, and centriolar satellite organization. Furthermore, we show that Wdr35 is essential for entry of many membrane proteins into the cilium through robust interactions with cargoes and other IFT-A subunits, but the actin network functions to dampen this transport. Wdr35 is mutated in several ciliopathies, and we find that certain disease mutations impair interactions with cargo and other IFT-A subunits. Together, our data link defects in IFT-A mediated cargo transport with disease.http://www.sciencedirect.com/science/article/pii/S2211124716314048WDR35IFT-Aciliaciliumcentrosomeciliary membraneArl13bactincargo transport |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wenxiang Fu Lei Wang Sehyun Kim Ji Li Brian David Dynlacht |
spellingShingle |
Wenxiang Fu Lei Wang Sehyun Kim Ji Li Brian David Dynlacht Role for the IFT-A Complex in Selective Transport to the Primary Cilium Cell Reports WDR35 IFT-A cilia cilium centrosome ciliary membrane Arl13b actin cargo transport |
author_facet |
Wenxiang Fu Lei Wang Sehyun Kim Ji Li Brian David Dynlacht |
author_sort |
Wenxiang Fu |
title |
Role for the IFT-A Complex in Selective Transport to the Primary Cilium |
title_short |
Role for the IFT-A Complex in Selective Transport to the Primary Cilium |
title_full |
Role for the IFT-A Complex in Selective Transport to the Primary Cilium |
title_fullStr |
Role for the IFT-A Complex in Selective Transport to the Primary Cilium |
title_full_unstemmed |
Role for the IFT-A Complex in Selective Transport to the Primary Cilium |
title_sort |
role for the ift-a complex in selective transport to the primary cilium |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2016-11-01 |
description |
Intraflagellar transport sub-complex A (IFT-A) is known to regulate retrograde IFT in the cilium. To rigorously assess its other possible roles, we knocked out an IFT-A subunit, IFT121/WDR35, in mammalian cells and screened the localization of more than 50 proteins. We found that Wdr35 regulates cilium assembly by selectively regulating transport of distinct cargoes. Beyond its role in retrograde transport, we show that Wdr35 functions in fusion of Rab8 vesicles at the nascent cilium, protein exit from the cilium, and centriolar satellite organization. Furthermore, we show that Wdr35 is essential for entry of many membrane proteins into the cilium through robust interactions with cargoes and other IFT-A subunits, but the actin network functions to dampen this transport. Wdr35 is mutated in several ciliopathies, and we find that certain disease mutations impair interactions with cargo and other IFT-A subunits. Together, our data link defects in IFT-A mediated cargo transport with disease. |
topic |
WDR35 IFT-A cilia cilium centrosome ciliary membrane Arl13b actin cargo transport |
url |
http://www.sciencedirect.com/science/article/pii/S2211124716314048 |
work_keys_str_mv |
AT wenxiangfu rolefortheiftacomplexinselectivetransporttotheprimarycilium AT leiwang rolefortheiftacomplexinselectivetransporttotheprimarycilium AT sehyunkim rolefortheiftacomplexinselectivetransporttotheprimarycilium AT jili rolefortheiftacomplexinselectivetransporttotheprimarycilium AT briandaviddynlacht rolefortheiftacomplexinselectivetransporttotheprimarycilium |
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1724995511843291136 |