Homo- and heterodimerization is a common feature of the solute carrier family SLC10 members.

Abstract:

: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.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Noppes S,Müller SF,Bennien J,Holtemeyer M,Palatini M,Leidolf R,Alber J,Geyer J

doi

10.1515/hsz-2019-0148

subject

Has Abstract

pub_date

2019-09-25 00:00:00

pages

1371-1384

issue

10

eissn

1431-6730

issn

1437-4315

pii

/j/bchm.ahead-of-print/hsz-2019-0148/hsz-2019-0148

journal_volume

400

pub_type

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