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, Kwang Meyung Kim, Ick Chan Kwon, In-San Kim, Sang Yoon Kim, Youngro Byun

Research output: Contribution to journalArticle

29 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
Externally publishedYes

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Macromolecular Substances
Membrane Transport Proteins
Endosomes
Exocytosis
Lysosomes
Bile Acids and Salts
Cell Membrane
sodium-bile acid cotransporter
bile acid binding proteins
Membranes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Al-Hilal, T. A., Chung, S. W., Alam, F., Park, J., Lee, K. E., Jeon, H., ... Byun, Y. (2014). Functional transformations of bile acid transporters induced by high-affinity macromolecules. Scientific Reports, 4, [4163]. https://doi.org/10.1038/srep04163

Functional transformations of bile acid transporters induced by high-affinity macromolecules. / Al-Hilal, Taslim A.; Chung, Seung Woo; Alam, Farzana; Park, Jooho; Lee, Kyung Eun; Jeon, Hyesung; Kim, Kwang Meyung; Kwon, Ick Chan; Kim, In-San; Kim, Sang Yoon; Byun, Youngro.

In: Scientific Reports, Vol. 4, 4163, 25.02.2014.

Research output: Contribution to journalArticle

Al-Hilal, TA, Chung, SW, Alam, F, Park, J, Lee, KE, Jeon, H, Kim, KM, Kwon, IC, Kim, I-S, Kim, SY & Byun, Y 2014, 'Functional transformations of bile acid transporters induced by high-affinity macromolecules', Scientific Reports, vol. 4, 4163. https://doi.org/10.1038/srep04163
Al-Hilal, Taslim A. ; Chung, Seung Woo ; Alam, Farzana ; Park, Jooho ; Lee, Kyung Eun ; Jeon, Hyesung ; Kim, Kwang Meyung ; Kwon, Ick Chan ; Kim, In-San ; Kim, Sang Yoon ; Byun, Youngro. / Functional transformations of bile acid transporters induced by high-affinity macromolecules. In: Scientific Reports. 2014 ; Vol. 4.
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