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bioRxiv · 10.1101/2025.01.02.631151

1,3- and 1,4-linked Polysaccharides Uptake in Intestinal Cells Relies on Clathrin/Dynamin 1/Rab5-dependent Endocytosis

Liao, W.·Cao, D.·Wang, Y.·Du, Z.·Yao, J.·Dou, P.·Zheng, Y.·Wang, Z.·Chen, X.·Wang, P.·Chen, H.·Diao, X.·Wang, K.·Ding, K.
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Abstract

Natural polysaccharides are considered to be a promising feedstock for manufacturing sustainable materials. However, polysaccharides are believed by most biologists that they could not be absorbed by intestinal mucosa to enter circulation system owing to their high hydrophilicity and large molecule size. Herein, {beta}-1,3-linked glucan (GFPBW1) and -1,4-linked glucan (WGE) is used as the model polysaccharide and the transport experiments show that different linked and charged polysaccharides can permeate Caco-2 cell monolayers. The in vivo experiments demonstrate that GFPBW1 and WGE are detectable in rodent plasma and liver after oral administration the isotope (99mTc, 3H) and fluorescein labeled polysaccharides. Further study show that polysaccharide uptake requires clathrin heavy chain (CLTC) and its associated factors Rab5 and dynamin1 in intestinal cells using gene-knockdown strategies and inhibitors. Strikingly, polysaccharide absorption is attenuated in both CLTC intestine deficient mice and Rab5, dynamin1 conventional-knockout mice. Importantly, membrane receptors bone morphogenetic protein receptor type IA (BMPRIA), Dectin-1 and epidermal growth factor receptor (EGFR) are also critical for specific structural polysaccharide internalization. These findings provide novel insight to understand polysaccharide absorption mechanism and lay foundation for oral polysaccharide- based new drugs development.

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Liao, W., Cao, D., Wang, Y., Du, Z., Yao, J., Dou, P., Zheng, Y., Wang, Z., Chen, X., Wang, P., Chen, H., Diao, X., Wang, K., Ding, K.. 2025-01-03. 1,3- and 1,4-linked Polysaccharides Uptake in Intestinal Cells Relies on Clathrin/Dynamin 1/Rab5-dependent Endocytosis. https://doi.org/10.1101/2025.01.02.631151

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