Functional transformations of bile acid transporters induced by high-affinity macromolecules

Taslim A. Al-Hilal, Seung Woo Chung, Farzana Alam, Jooho Park, Kyung Eun Lee, Hyesung Jeon, Kwangmeyung Kim, Ick Chan Kwon, In San Kim, Sang Yoon Kim, Youngro Byun

    Research output: Contribution to journalArticlepeer-review

    52 Citations (Scopus)

    Abstract

    Apical sodium-dependent bile acid transporters (ASBT) are the intestinal transporters that form intermediate complexes with substrates and its conformational change drives the movement of substrates across the cell membrane. However, membrane-based intestinal transporters are confined to the transport of only small molecular substrates. Here, we propose a new strategy that uses high-affinity binding macromolecular substrates to functionally transform the membrane transporters so that they behave like receptors, ultimately allowing the apical-basal transport of bound macromolecules. Bile acid based macromolecular substrates were synthesized and allowed to interact with ASBT. ASBT/macromolecular substrate complexes were rapidly internalized in vesicles, localized in early endosomes, dissociated and escaped the vesicular transport while binding of cytoplasmic ileal bile acid binding proteins cause exocytosis of macromolecules and prevented entry into lysosomes. This newly found transformation process of ASBT suggests a new transport mechanism that could aid in further utilization of ASBT to mediate oral macromolecular drug delivery.

    Original languageEnglish
    Article number4163
    JournalScientific reports
    Volume4
    DOIs
    Publication statusPublished - 2014 Feb 25

    Bibliographical note

    Funding Information:
    We thank S.M. Riajul Wahab for the collaboration in molecular biology works and Ms Eun Jung Kang for the technical supports with confocal imaging. This study was supported by a grant from the World Class University (WCU) program (grant no. R31-2008-000-10103), the Converging Research Center Program (grant no. 2012K-001398) and the Bio & Medical Technology Development Program (grant no. 2012028833) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, Republic of Korea and Mediplex Corp., Korea.

    ASJC Scopus subject areas

    • General

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