Filatova, Alina and Leyerer, Marina and Gorboulev, Valentin and Chintalapati, Chakravarthi and Reinders, Yvonne and Mueller, Thomas D. and Srinivasan, Aruna and Huebner, Stefan and Koepsell, Hermann (2009) Novel Shuttling Domain in a Regulator (RSC1A1) of Transporter SGLT1 Steers Cell Cycle-Dependent Nuclear Location. TRAFFIC, 10 (11). pp. 1599-1618. ISSN 1398-9219, 1600-0854
Full text not available from this repository. (Request a copy)Abstract
The gene product of RSC1A1, RS1, participates in the regulation of the Na+-D-glucose cotransporter SGLT1. RS1 inhibits release of SGLT1 from the trans Golgi network. In subconfluent LLC-PK1 cells, RS1 migrates into the nucleus and modulates transcription of SGLT1, whereas most confluent cells do not contain RS1 in the nuclei. We showed that confluence-dependent nuclear location of RS1 is because of different phases of the cell cycle and identified a RS1 nuclear shuttling domain (RNS) with an associated protein kinase C (PKC) phosphorylation site (RNS-PKC) that mediates cell cycle-dependent nuclear location. RNS-PKC contains a novel non-conventional nuclear localization signal interacting with importin beta 1, a nuclear export signal mediating export via protein CRM1 and a Ca2+-dependent calmodulin binding site. PKC and calmodulin compete for binding to RNS-PKC. Mutagenesis experiments and analyses of the phosphorylation status suggest the following sequences of events. Subconfluent cells without and with synchronization to the G2/M phase contain non-phosphorylated RNS-PKC that mediates nuclear import of RS1 but not its export. During confluence or synchronization of subconfluent cells to the G2/M phase, phosphorylation of RNS-PKC mediates rapid nuclear export of RS1.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-KINASE-C; D-GLUCOSE COTRANSPORTER; MEMBRANE-ASSOCIATED PROTEIN; RS1 RSC1A1; LLC-PK1 CELLS; INTRACELLULAR CALCIUM; LOCALIZATION SIGNALS; EXOCYTOTIC PATHWAY; CRYSTAL-STRUCTURE; SEQUENCE MOTIFS; calmodulin binding motif; cell cycle; confluence; nuclear export signal; nuclear localization signal; nuclear shuttling signal; regulation; RSI; SGLT1; sodium-D-glucose cotransport |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Sep 2020 04:54 |
| Last Modified: | 03 Sep 2020 04:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28244 |
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