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The NTCP (Na⁺-taurocholate co-transporting protein)/SLC10A [solute carrier family 10 (Nav/bile acid co-transporter family)] 1 is tightly controlled to ensure hepatic bile salt uptake while preventing toxic bile salt accumulation. Many transport proteins require oligomerization for their activity and regulation. This is not yet established for bile salt transporters. The present study was conducted to elucidate the oligomeric state of NTCP. Chemical cross-linking revealed the presence of NTCP dimers in rat liver membranes and U2OS cells stably expressing NTCP. Co-immunoprecipitation of tagged NTCP proteins revealed a physical interaction between subunits. The C-terminus of NTCP was not required for subunit interaction, but was essential for exit from the ER (endoplasmic reticulum). NTCP without its C-terminus (NTCP Y307X) retained full-length wtNTCP (wild-type NTCP) in the ER in a dominant fashion, suggesting that dimerization occurs early in the secretory pathway. FRET (fluorescence resonance energy transfer) using fluorescently labelled subunits further demonstrated that dimerization persists at the plasma membrane. NTCP belongs to the SLC10A protein family which consists of seven members. NTCP co-localized in U2OS cells with SLC10A4 and SLC10A6, but not with SLC10A3, SLC10A5 or SLC10A7. SLC10A4 and SLC10A6 co-immunoprecipitated with NTCP, demonstrating that heteromeric complexes can be formed between SLC10A family members in vitro. Expression of SLC10A4 and NTCP Y307X resulted in a reduction of NTCP abundance at the plasma membrane and NTCP-mediated taurocholate uptake, whereas expression of SLC10A6 or NTCP E257N, an inactive mutant, did not affect NTCP function. In conclusion, NTCP adopts a dimeric structure in which individual subunits are functional. Bile salt uptake is influenced by heterodimerization when this impairs NTCP plasma membrane trafficking.

No abstract

A flipped classroom, an approach abandoning traditional lectures and having students come together to apply acquired knowledge, requires students to come to class well prepared. The nature of this preparation is currently being debated. Watching web lectures as a preparation has typically been recommended, but more recently, a variety of study materials has been considered to serve students personal learning preferences. The aim of this study was to explore in two flipped courses which online study materials stimulate students most to prepare for in-class activities, to find out whether students differ in their use of study materials, and to explore how students use of online study materials relates to their learning strategies. In a basic science and a clinical course, medical students were provided with web lectures, text selections, scientific papers, books, and formative test questions or case studies. Use of these online materials was determined with questionnaires. All students watched web lectures and read text selections to prepare for in-class activities, but students differed in the extent to which they used more challenging materials. Additionally, the use of online study materials was related to students' learning strategies that involved regulation and monitoring of study effort. Our findings suggest that students have similar learning preferences as they all use the same "basic materials" to prepare for in-class activities. We interpret the preferential use of web lectures and text selections as being regarded as sufficient for active in-class participation. The less intensive use of other study materials may reflect students' perception of limited study time.

Students using online formative tests linked to microlectures receive higher grades especially in highly aligned summative tests.