Calcium Influx Promotes PLEKHG4B Localization to Cell-cell Junctions and Regulates the Integrity of Junctional Actin Filaments

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2023 Dec 13

PMID 38088892

Authors

Komaki Ninomiya

Kai Ohta

Ukyo Kawasaki

Shuhei Chiba

Takanari Inoue

Erina Kuranaga

Kazumasa Ohashi

Kensaku Mizuno

Affiliations

Soon will be listed here.

Abstract

PLEKHG4B is a Cdc42-targeting guanine-nucleotide exchange factor implicated in forming epithelial cell-cell junctions. Here we explored the mechanism regulating PLEKHG4B localization. PLEKHG4B localized to the basal membrane in normal Ca medium but accumulated at cell-cell junctions upon ionomycin treatment. Ionomycin-induced junctional localization of PLEKHG4B was suppressed upon disrupting its annexin-A2 (ANXA2)-binding ability. Thus, Ca influx and ANXA2 binding are crucial for PLEKHG4B localization to cell-cell junctions. Treatments with low Ca or BAPTA-AM (an intracellular Ca chelator) suppressed PLEKHG4B localization to the basal membrane. Mutations of the phosphoinositide-binding motif in the pleckstrin homology (PH) domain of PLEKHG4B or masking of membrane phosphatidylinositol-4,5-biphosphate [PI(4,5)P] suppressed PLEKHG4B localization to the basal membrane, indicating that basal membrane localization of PLEKHG4B requires suitable intracellular Ca levels and PI(4,5)P binding of the PH domain. Activation of mechanosensitive ion channels (MSCs) promoted PLEKHG4B localization to cell-cell junctions, and their inhibition suppressed it. Moreover, similar to the PLEKHG4B knockdown phenotypes, inhibition of MSCs or treatment with BAPTA-AM disturbed the integrity of actin filaments at cell-cell junctions. Taken together, our results suggest that Ca influx plays crucial roles in PLEKHG4B localization to cell-cell junctions and the integrity of junctional actin organization, with MSCs contributing to this process.

Citing Articles

Roles of the Dbl family of RhoGEFs in mechanotransduction - a review.

Ohashi K, Kunitomi A, Chiba S, Mizuno K Front Cell Dev Biol. 2024; 12:1485725.

PMID: 39479515 PMC: 11521908. DOI: 10.3389/fcell.2024.1485725.

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