The nucleocytoplasmic translocation of HINT1 regulates the maturation of cell density
Xiaofang Zhang, Fumihiko Nakamura
TL;DR
HINT1 moves between the nucleus and cytoplasm depending on cell density, regulating transcription and actin remodeling to control cell maturation.
Contribution
HINT1 is identified as a dual-function regulator of cell maturation through nucleocytoplasmic shuttling.
Findings
HINT1 localizes in the nucleus at low density and binds to open chromatin.
At high density, HINT1 translocates to the cytoplasm and modulates actin remodeling.
HINT1 is required for full cell confinement and mature monolayer formation.
Abstract
HINT1’s density-dependent shuttling regulates nuclear transcription at low density and cytoplasmic actin remodeling at high density. In normal epithelial cells on tissue culture dishes, contact inhibition typically progresses with a reduction in cell size after cell–cell contact. This transition involves actin cytoskeleton reorganization from stress fibers (SFs) to a cortical network, stabilizing cell shape and strengthening connections. However, the regulatory signaling pathways remain unclear. We identified histidine triad nucleotide-binding protein 1 (HINT1), also known as protein kinase C inhibitor 1 (PKCI-1), as a regulator for monolayer maturation. At low density, HINT1 localizes in the nucleus and binds to open chromatin. As density increases, exportin 1 drives HINT1 translocation to the cytoplasm. Forced cytoplasmic localization of HINT1 reduces phosphorylation of myristoylated…
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Taxonomy
TopicsHippo pathway signaling and YAP/TAZ · Cellular Mechanics and Interactions · Wnt/β-catenin signaling in development and cancer