| First Author | Yasuda T | Year | 2014 |
| Journal | J Cell Sci | Volume | 127 |
| Issue | Pt 3 | Pages | 557-70 |
| PubMed ID | 24284068 | Mgi Jnum | J:211887 |
| Mgi Id | MGI:5576844 | Doi | 10.1242/jcs.134056 |
| Citation | Yasuda T, et al. (2014) Slp2-a controls renal epithelial cell size through regulation of Rap-ezrin signaling independently of Rab27. J Cell Sci 127(Pt 3):557-70 |
| abstractText | Synaptotagmin-like protein 2 (Slp2-a/Sytl2) is a Rab27 effector protein that regulates transport of Rab27-bearing vesicles and organelles through its N-terminal Rab27-binding domain and a phospholipid-binding C2A domain. Here we demonstrate a Rab27-independent function of Slp2-a in the control of renal cell size through a previously uncharacterized C2B domain. We found that by recruiting Rap1 GAPs to the plasma membrane of MDCK II cells through the C2B domain, Slp2-a inactivates Rap signaling and modulates the size of the cells. Functional ablation of Slp2-a resulted in an increase in the size of MDCK II cells. Drosophila Slp Bitesize was found to compensate for the function of Slp2-a in MDCK II cells, thereby indicating that the mechanism of the cell size control by Slp proteins has been evolutionarily conserved. Interestingly, blockade of the activity of ezrin, a downstream target of Rap, with the glucosylceramide synthase inhibitor, miglustat, effectively inhibited cell spreading of Slp2-a-knockdown cells. We also discovered aberrant expression of Slp2-a and increased activity of ezrin in pcy (Nphp3(pcy)) mice, a model of polycystic kidney disease that is characterized by renal cell spreading. Our findings indicate that Slp2-a controls renal cell size through regulation of Rap-ezrin signaling independently of Rab27. |
