Al-Hilal, Taslim A. Chung, Seung Woo Alam, Farzana Park, Jooho Lee, Kyung Eun Jeon, Hyesung Kim, Kwangmeyung Kwon, Ick Chan Kim, In-San Kim, Sang Yoon Byun, Youngro 2024-01-20T10:30:54Z 2024-01-20T10:30:54Z 2021-09-05 2014-02-25 2045-2322 https://pubs.kist.re.kr/handle/201004/127079 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. English NATURE PUBLISHING GROUP ORAL-DRUG DELIVERY MEMBRANE CURVATURE MECHANISMS PROTEIN COLOCALIZATION CHOLANGIOCYTES EXPRESSION PATHWAYS ASBT Functional transformations of bile acid transporters induced by high-affinity macromolecules Article 10.1038/srep04163 1 SCIENTIFIC REPORTS, v.4 SCIENTIFIC REPORTS 4 scie scopus 000331886500001 2-s2.0-84894816912 Multidisciplinary Sciences Science & Technology - Other Topics Article ORAL-DRUG DELIVERY MEMBRANE CURVATURE MECHANISMS PROTEIN COLOCALIZATION CHOLANGIOCYTES EXPRESSION PATHWAYS ASBT