LTBP3

LTBP3, or latent TGF-β binding protein 3, is a secreted extracellular matrix glycoprotein that belongs to the latent TGF-β binding protein family. It participates in the sequestration and regulation of latent transforming growth factor beta (TGF-β) within the extracellular matrix, contributing to the spatial control of TGF-β signaling during development and tissue maintenance.

Function and mechanism

LTBP3 is thought to associate with the large latent complex of TGF-β, helping to tether it to extracellular matrix components and to fibrillin-containing microfibrils. This positioning influences the availability and activation of TGF-β in a tissue-specific context. Activation of latent TGF-β can occur through mechanical forces, proteolysis, or interactions with other ECM proteins, and LTBP3 is implicated in modulating how readily TGF-β signaling is initiated in different cellular environments.

Structure and interactions

LTBP3 is a modular secreted protein containing domains characteristic of the LTBP family, including regions that mediate protein–protein interactions. It interacts with components of the extracellular matrix, notably fibrillin-1, which helps anchor latent TGF-β complexes within the ECM. Through these interactions, LTBP3 contributes to the assembly and organization of the ECM as well as to the regulation of signaling pathways linked to TGF-β.

Expression, development, and disease

LTBP3 is expressed in many tissues and is involved in developmental processes that rely on TGF-β signaling, such as skeletal, dental, and craniofacial formation. In animal models, disruption of LTBP3 can lead to skeletal or dental abnormalities and altered ECM structure, suggesting a role in normal morphogenesis and tissue homeostasis. In humans, rare mutations or dysregulation of LTBP3 have been linked to phenotypes involving craniofacial and dental development, though the full spectrum of clinical effects continues to be investigated.

Research and context

LTBP3 is studied to understand how latent TGF-β is stored and activated in the ECM and how ECM organization intersects with growth factor signaling. It is one of several LTBPs that coordinate the extracellular storage and activation of TGF-β across tissues.