A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes
The sensory functions of cilia are dependent on the enrichment of cilium-resident proteins. Although it is known that ciliary targeting signals (CTSs) specifically target ciliary proteins to cilia, it is still unclear how CTSs facilitate the entry and retention of cilium-resident proteins at the mol...
| Main Authors: | , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2017
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| Online Access: | https://hdl.handle.net/10356/84044 http://hdl.handle.net/10220/42908 |
| _version_ | 1811688862439702528 |
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| author | Madugula, Viswanadh Lu, Lei |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Madugula, Viswanadh Lu, Lei |
| author_sort | Madugula, Viswanadh |
| collection | NTU |
| description | The sensory functions of cilia are dependent on the enrichment of cilium-resident proteins. Although it is known that ciliary targeting signals (CTSs) specifically target ciliary proteins to cilia, it is still unclear how CTSs facilitate the entry and retention of cilium-resident proteins at the molecular level. We found that non-ciliary membrane reporters can passively diffuse into cilia through the lateral transport pathway, and the translocation of membrane reporters through the ciliary diffusion barrier is facilitated by importin binding motifs and domains. Screening known CTSs of ciliary membrane residents uncovered that fibrocystin, photoreceptor retinol dehydrogenase, rhodopsin and retinitis pigmentosa 2 interact with transportin1 (TNPO1) through previously identified CTSs. We further discovered that a new ternary complex, comprising TNPO1, Rab8 and a CTS, can assemble or disassemble under the guanine nucleotide exchange activity of Rab8. Our study suggests a new mechanism in which the TNPO1–Rab8–CTS complex mediates selective entry into and retention of cargos within cilia. |
| first_indexed | 2024-10-01T05:38:57Z |
| format | Journal Article |
| id | ntu-10356/84044 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:38:57Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/840442023-02-28T17:04:29Z A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes Madugula, Viswanadh Lu, Lei School of Biological Sciences Cilia Transportin1 The sensory functions of cilia are dependent on the enrichment of cilium-resident proteins. Although it is known that ciliary targeting signals (CTSs) specifically target ciliary proteins to cilia, it is still unclear how CTSs facilitate the entry and retention of cilium-resident proteins at the molecular level. We found that non-ciliary membrane reporters can passively diffuse into cilia through the lateral transport pathway, and the translocation of membrane reporters through the ciliary diffusion barrier is facilitated by importin binding motifs and domains. Screening known CTSs of ciliary membrane residents uncovered that fibrocystin, photoreceptor retinol dehydrogenase, rhodopsin and retinitis pigmentosa 2 interact with transportin1 (TNPO1) through previously identified CTSs. We further discovered that a new ternary complex, comprising TNPO1, Rab8 and a CTS, can assemble or disassemble under the guanine nucleotide exchange activity of Rab8. Our study suggests a new mechanism in which the TNPO1–Rab8–CTS complex mediates selective entry into and retention of cargos within cilia. MOE (Min. of Education, S’pore) NMRC (Natl Medical Research Council, S’pore) Published version 2017-07-18T07:00:43Z 2019-12-06T15:37:07Z 2017-07-18T07:00:43Z 2019-12-06T15:37:07Z 2016 Journal Article Madugula, V., & Lu, L. (2016). A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes. Journal of Cell Science, 129(20), 3922-3934. 0021-9533 https://hdl.handle.net/10356/84044 http://hdl.handle.net/10220/42908 10.1242/jcs.194019 27633000 en Journal of Cell Science © 2016 The Author(s). Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. 13 p. application/pdf |
| spellingShingle | Cilia Transportin1 Madugula, Viswanadh Lu, Lei A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes |
| title | A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes |
| title_full | A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes |
| title_fullStr | A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes |
| title_full_unstemmed | A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes |
| title_short | A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes |
| title_sort | ternary complex comprising transportin1 rab8 and the ciliary targeting signal directs proteins to ciliary membranes |
| topic | Cilia Transportin1 |
| url | https://hdl.handle.net/10356/84044 http://hdl.handle.net/10220/42908 |
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