| First Author | Srivastava S | Year | 2019 |
| Journal | J Physiol Sci | Volume | 69 |
| Issue | 2 | Pages | 399-408 |
| PubMed ID | 30604288 | Mgi Jnum | J:334002 |
| Mgi Id | MGI:7444875 | Doi | 10.1007/s12576-018-00658-1 |
| Citation | Srivastava S, et al. (2019) Identification of the multivalent PDZ protein PDZK1 as a binding partner of sodium-coupled monocarboxylate transporter SMCT1 (SLC5A8) and SMCT2 (SLC5A12). J Physiol Sci 69(2):399-408 |
| abstractText | Sodium-coupled monocarboxylate transporters SMCT1 (SLC5A8) and SMCT2 (SLC5A12) mediate the high- and low-affinity transport of lactate in the kidney, but their regulatory mechanism is still unknown. Since these two transporters have the PDZ-motif at their C-terminus, the function of SMCTs may be modulated by a protein-protein interaction. To investigate the binding partner(s) of SMCTs in the kidney, we performed yeast two-hybrid (Y2H) screenings of a human kidney cDNA library with the C-terminus of SMCT1 (SMCT1-CT) and SMCT2 (SMCT2-CT) as bait. PDZK1 was identified as a partner for SMCTs. PDZK1 coexpression in SMCT1-expressing HEK293 cells enhanced their nicotinate transport activity. PDZK1, SMCT1, and URAT1 in vitro assembled into a single tri-molecular complex and their colocalization was confirmed in the renal proximal tubule in vivo by immunohistochemistry. These results indicate that the SMCT1-PDZK1 interaction thus plays an important role in both lactate handling as well as urate reabsorption in the human kidney. |