Clathrin-coated tubules mediate rapid and selective protein absorption by lysosome-rich enterocytes
Abstract
In the digestive tract of neonatal mammals and in fish, lysosome-rich enterocytes (LREs) internalize dietary proteins and digest them intracellularly within a large lysosomal vacuole. Impaired LRE function leads to growth stunting and poor survival in zebrafish and mice. Previous work has shown that protein uptake relies on a scavenger receptor complex. However, how LREs can internalize proteins rapidly enough to support organismal growth is unclear. Here, using live and electron microscopy and genetic manipulations in zebrafish, we find that LREs contain apical micron-sized clathrin-coated endocytic tubules (ETs) that perform rapid internalization of proteins and other soluble cargoes, while excluding resident apical membrane proteins. Dab2, an endocytic adaptor linking clathrin to scavenger receptors, controls both the biogenesis and function of ETs by recruiting unconventional myosin Myo6 and by influencing dynamin activity. Our findings suggest that continuous pinching of vesicles from ETs allows for rapid, high-capacity internalization of dietary protein.
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BibTeX
@misc{magre2026clathrincoated,
title = {{Clathrin-coated tubules mediate rapid and selective protein absorption by lysosome-rich enterocytes}},
author = {Indrasen Magre and Tylor R. Lewis and Claudia Carugati and Carina L. Block and Siyao Wang and Kevin Li and Jieun Park and Vadim Y. Arshavsky and Daniel S Levic and Michel Bagnat},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.22.761028},
url = {https://www.biorxiv.org/content/10.64898/2026.10.22.761028v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Clathrin-coated tubules mediate rapid and selective protein absorption by lysosome-rich enterocytes
AU - Indrasen Magre
AU - Tylor R. Lewis
AU - Claudia Carugati
AU - Carina L. Block
AU - Siyao Wang
AU - Kevin Li
AU - Jieun Park
AU - Vadim Y. Arshavsky
AU - Daniel S Levic
AU - Michel Bagnat
PY - 2026
DA - 2026/10/22
PB - bioRxiv
DO - 10.64898/2026.10.22.761028
UR - https://www.biorxiv.org/content/10.64898/2026.10.22.761028v1
AB - In the digestive tract of neonatal mammals and in fish, lysosome-rich enterocytes (LREs) internalize dietary proteins and digest them intracellularly within a large lysosomal vacuole. Impaired LRE function leads to growth stunting and poor survival in zebrafish and mice. Previous work has shown that protein uptake relies on a scavenger receptor complex. However, how LREs can internalize proteins rapidly enough to support organismal growth is unclear. Here, using live and electron microscopy and genetic manipulations in zebrafish, we find that LREs contain apical micron-sized clathrin-coated endocytic tubules (ETs) that perform rapid internalization of proteins and other soluble cargoes, while excluding resident apical membrane proteins. Dab2, an endocytic adaptor linking clathrin to scavenger receptors, controls both the biogenesis and function of ETs by recruiting unconventional myosin Myo6 and by influencing dynamin activity. Our findings suggest that continuous pinching of vesicles from ETs allows for rapid, high-capacity internalization of dietary protein.
SN - 2692-8205
ER -