A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells
Selective protein distribution on distinct plasma membranes is important for epithelial cell function. To date, how proteins are directed to specific epithelial cell surface is not fully understood. Here we report a conserved DSSDE motif in LDL-receptor (LDLR) modules of corin (a transmembrane serin...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/56059 |
| _version_ | 1828375916987809792 |
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| author | Ce Zhang Yue Chen Shijin Sun Yikai Zhang Lina Wang Zhipu Luo Meng Liu Liang Dong Ningzheng Dong Qingyu Wu |
| author_facet | Ce Zhang Yue Chen Shijin Sun Yikai Zhang Lina Wang Zhipu Luo Meng Liu Liang Dong Ningzheng Dong Qingyu Wu |
| author_sort | Ce Zhang |
| collection | DOAJ |
| description | Selective protein distribution on distinct plasma membranes is important for epithelial cell function. To date, how proteins are directed to specific epithelial cell surface is not fully understood. Here we report a conserved DSSDE motif in LDL-receptor (LDLR) modules of corin (a transmembrane serine protease) and CD320 (a receptor for vitamin B12 uptake), which regulates apical membrane targeting in renal epithelial cells. Altering this motif prevents specific apical corin and CD320 expression in polarized Madin–Darby canine kidney (MDCK) cells. Mechanistic studies indicate that this DSSDE motif participates in a Rab11a-dependent mechanism that specifies apical sorting. In MDCK cells, inhibition of Rab11a, but not Rab11b, expression leads to corin and CD320 expression on both apical and basolateral membranes. Together, our results reveal a novel molecular recognition mechanism that regulates LDLR module-containing proteins in their specific apical expression in polarized renal epithelial cells. |
| first_indexed | 2024-04-14T07:53:33Z |
| format | Article |
| id | doaj.art-33b2e468201d4f75ac7a90cb9c2c2c67 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:53:33Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-33b2e468201d4f75ac7a90cb9c2c2c672022-12-22T02:05:08ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.56059A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cellsCe Zhang0Yue Chen1Shijin Sun2Yikai Zhang3Lina Wang4Zhipu Luo5Meng Liu6Liang Dong7Ningzheng Dong8Qingyu Wu9https://orcid.org/0000-0003-0561-9315Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China; MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China; MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaInstitute of Molecular Enzymology, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China; MOH Key Laboratory of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China; Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, United StatesSelective protein distribution on distinct plasma membranes is important for epithelial cell function. To date, how proteins are directed to specific epithelial cell surface is not fully understood. Here we report a conserved DSSDE motif in LDL-receptor (LDLR) modules of corin (a transmembrane serine protease) and CD320 (a receptor for vitamin B12 uptake), which regulates apical membrane targeting in renal epithelial cells. Altering this motif prevents specific apical corin and CD320 expression in polarized Madin–Darby canine kidney (MDCK) cells. Mechanistic studies indicate that this DSSDE motif participates in a Rab11a-dependent mechanism that specifies apical sorting. In MDCK cells, inhibition of Rab11a, but not Rab11b, expression leads to corin and CD320 expression on both apical and basolateral membranes. Together, our results reveal a novel molecular recognition mechanism that regulates LDLR module-containing proteins in their specific apical expression in polarized renal epithelial cells.https://elifesciences.org/articles/56059apical expressionCD320corinldl receptor moduleRab11a |
| spellingShingle | Ce Zhang Yue Chen Shijin Sun Yikai Zhang Lina Wang Zhipu Luo Meng Liu Liang Dong Ningzheng Dong Qingyu Wu A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells eLife apical expression CD320 corin ldl receptor module Rab11a |
| title | A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells |
| title_full | A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells |
| title_fullStr | A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells |
| title_full_unstemmed | A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells |
| title_short | A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells |
| title_sort | conserved ldl receptor motif regulates corin and cd320 membrane targeting in polarized renal epithelial cells |
| topic | apical expression CD320 corin ldl receptor module Rab11a |
| url | https://elifesciences.org/articles/56059 |
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