Transmembrane Protein-184A Interacts with Syndecan-4 and Rab GTPases and Is Required to Maintain VE-Cadherin Levels

TL;DR

This study shows how TMEM184A interacts with Sdc4 to regulate VE-cadherin levels and vascular cell functions.

Contribution

The novel contribution is identifying TMEM184A's dual role in signaling and trafficking to maintain VE-cadherin in vascular cells.

Findings

TMEM184A and Sdc4 colocalize and cooperate in angiogenesis and tissue repair.

siTMEM reduces VE-cad levels but increases wound migration rates.

TMEM overexpression enhances VE-cad trafficking and membrane recovery.

Abstract

VE-cadherin (VE-cad) membrane stability and localization regulates adhesion formation and actin cytoskeleton dynamics in angiogenesis and vascular remodeling and requires the heparan sulfate proteoglycan (HSPG), Syndecan-4 (Sdc4). This study characterizes the interactions of the heparin receptor, Transmembrane protein-184A (TMEM184A), and Sdc4 in bovine aortic endothelial cells (BAOECs) and the regenerating Zebrafish (ZF) caudal fin and measures the effect of siRNA TMEM184A KD (siTMEM) and TMEM184A overexpression (TMEM OE) on VE-cad levels and localization in confluent and sub-confluent cultured BAOECs. Additionally, we examined the effect of siTMEM on key Rab GTPase trafficking regulators and migrating BAOECs in scratch wound healing assays. We demonstrated that TMEM184A and Sdc4 colocalize in BAOECs and that Sdc4 OE increases colocalization in an HS chain dependent manner, while both Tmem184a and Sdc4 cooperate synergistically in ZF fin angiogenic and tissue repair. We also showed that siTMEM decreases VE-cad membrane and cytoplasmic levels, while increasing scratch wound migration rates. However, TMEM OE cells show increased vesicle formation and VE-cad trafficking and membrane recovery. These findings characterize TMEM184A-Sdc4 cooperation in angiogenesis and indicate a dual function of TMEM184A in signaling and trafficking in vascular cells that promotes VE-cad recovery and membrane localization.

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