ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin
Volume
12
Publisher
DOI
10.7554/elife.89261.3
Journal
eLife
ISSN
2050-084X
Metadata
Show full item recordAbstract
Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with,
and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical
membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells
but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells,
liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1
regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals
to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics
and size of bile canalicular-like structures. We identified the scaffolding protein EBP50/NHERF1/
SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli,
from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for
ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1
regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell–
cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress.