Extracellular TG2: emerging functions and regulation

Extracellular TG2: Emerging Functions and Regulation

Author: Alexey M. Belkin

Field: Biochemistry and Molecular Biology

Document Content:

This review explores the multifaceted roles and dynamic regulation of extracellular Transglutaminase 2 (TG2), a member of the Ca2+-dependent crosslinking enzyme family. While TG2 possesses enzymatic functions like transamidation, evidence has increasingly highlighted its significant involvement in cell-surface and extracellular matrix (ECM) processes. These encompass regulating cell-ECM interactions and mediating signaling through transmembrane receptors. The document details recent research on TG2’s emerging functions beyond its crosslinking activity, focusing on its non-enzymatic roles. It examines how TG2 interacts with key players like integrins, fibronectin, and syndecan-4, influencing cell adhesion, migration, and signaling pathways. Furthermore, the review delves into TG2’s interactions with growth factor receptors and its role in inducing β-catenin signaling via LRP5/6 receptors. The dynamic regulation of extracellular TG2 is discussed, including unconventional secretion pathways, internalization mechanisms involving LRP1, and its susceptibility to pericellular proteolysis by matrix metalloproteinases. These findings collectively underscore the importance of TG2 in various pathophysiological conditions, suggesting it as a potential therapeutic target.

Table of Contents:

• Introduction
• Extracellular TG2: enzymatic and non-enzymatic functions
• Adhesive/signaling functions of extracellular TG2
• Integrin-TG2 interaction and its role in cell-ECM adhesion and signaling
• Syndecan-4-TG2 complexes on the cell surface: a parallel adhesive/signaling platform
• Cell surface TG2 as a new regulator of joint integrin/growth factor receptor signaling
• Extracellular TG2 acts through LRP5/6 transmembrane receptors to induce β-catenin signaling
• Other interacting partners of extracellular TG2
• Dynamic regulation of extracellular TG2
• Unconventional secretion of TG2
• The balance between cell surface and matrix TG2: what is the translocation mechanism?
• Internalization of TG2 from the cell surface
• Pericellular proteolysis controls the fate of extracellular TG2
• Conclusions