Vai Hong FongShaun WongPonrutsami JintaridhiAmandio VieiraSimon Fraser UniversityMahidol UniversityFar Eastern Memory Hospital2020-01-272020-01-272019-01-01Endocrine Research. (2019)15324206074358002-s2.0-85075540082https://repository.li.mahidol.ac.th/handle/20.500.14594/50343© 2019, © 2019 Taylor & Francis Group, LLC. Purpose: Transthyretin (TTR) is a protein with a growing number of biological functions in addition to its well-established binding and circulatory transport of thyroxine, and indirect retinoid transport through interaction with retinol-binding protein. Misfolded and aggregated wild-type and mutant TTRs are involved in amyloid diseases. Several aspects of TTR pathology and physiology remain poorly understood. Receptor-mediated cellular transport of TTR has been described in a few cell types; and such studies suggest the possibility of different TTR receptors and endocytic pathways. Our main objective was to further understand the endocytic pathways for TTR. Methods: In the current study, analyses of TTR endocytic transport were performed in the human A431 cell line. The results of TTR uptake were compared with those of the iron-carrier protein transferrin (Tf, a common stardard for endocytosis studies) in the same cell types. Results: A comparison of TTR and Tf endocytosis suggested similar early, 5–10 min, accumulation kinetics. But at a later time, 30 min, TTR accumulation was 20-30% lower than that of Tf (p < .05), a result that suggests different post-endocytic fates for these two ligands. Through the use of multiple endocytosis inhibitors, biochemical evidence is provided for an internalization pathway that differs from the clathrin-mediated endocytosis of Tf. Conclusions: These results for A431 cells are compared with others reported for different cell types; and it is suggested that this same hormone carrier protein can transit into cells through multiple endocytic pathways.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1080/07435800.2019.1694538