Homo- and heterodimerization is a common feature of the solute carrier family SLC10 members
| Autor: | Matthias Holtemeyer, J. Alber, Regina Leidolf, Simon Franz Müller, Joachim Geyer, Josefine Bennien, Massimo Palatini, Saskia Noppes |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.drug_class Two-hybrid screening Clinical Biochemistry Organic Anion Transporters Sodium-Dependent medicine.disease_cause digestive system Biochemistry 03 medical and health sciences 0302 clinical medicine Protein targeting medicine Animals Humans Steroid sulfate Molecular Biology Bile acid Chemistry Sodium Biological Transport Transporter Solute carrier family 030104 developmental biology Membrane protein Biophysics Dimerization 030217 neurology & neurosurgery Function (biology) |
| Zdroj: | Biological Chemistry. 400:1371-1384 |
| ISSN: | 1437-4315 1431-6730 |
| Popis: | The solute carrier family SLC10 consists of seven members, including the bile acid transporters Na+/taurocholate co-transporting polypeptide (NTCP) and apical sodium-dependent bile acid transporter (ASBT), the steroid sulfate transporter SOAT as well as four orphan carriers (SLC10A3, SLC10A4, SLC10A5 and SLC10A7). Previously, homodimerization of NTCP, ASBT and SOAT was described and there is increasing evidence that carrier oligomerization is an important regulatory factor for protein sorting and transport function. In the present study, homo- and heterodimerization were systematically analyzed among all SLC10 carriers (except for SLC10A3) using the yeast-two-hybrid membrane protein system. Strong homodimerization occurred for NTCP/NTCP, ASBT/ASBT and SLC10A7/SLC10A7. Heterodimerization was observed for most of the SLC10 carrier combinations. Heterodimerization of NTCP was additionally investigated by co-localization of NTCP-GFP and NTCP-mScarlet with respective SLC10 carrier constructs. NTCP co-localized with SLC10A4, SLC10A5, SOAT and SLC10A7. This co-localization was most pronounced for SLC10A4 and was additionally confirmed by co-immunoprecipitation. Interestingly, SLC10 carrier co-expression decreased the taurocholate transport function of NTCP for most of the analyzed constructs, indicating that SLC10 carrier heterodimerization is of functional relevance. In conclusion, homo- and heterodimerization is a common feature of the SLC10 carriers. The relevance of this finding for regulation and transport function of the SLC10 carriers in vivo needs further investigation. |
| Databáze: | OpenAIRE |
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