Latent TGF-β-binding proteins

• Published in: Matrix biology Vol. 47; pp. 44 - 53
• Main Authors: Robertson, Ian B., Horiguchi, Masahito, Zilberberg, Lior, Dabovic, Branka, Hadjiolova, Krassimira, Rifkin, Daniel B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2015
• Subjects: Animals; Extracellular matrix; Extracellular Matrix - physiology; Fibrillins; Humans; Latency associated protein; Latent TGF-beta Binding Proteins - physiology; Latent TGFβ binding proteins; Microfilament Proteins - physiology; Protein Isoforms - physiology; Signal Transduction; TGFβ activation; Transforming Growth Factor beta - physiology; Extracellular matrix; Latency associated protein; TGFβ activation; Latent TGFβ binding proteins
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2015.05.005

The LTBPs (or latent transforming growth factor β binding proteins) are important components of the extracellular matrix (ECM) that interact with fibrillin microfibrils and have a number of different roles in microfibril biology. There are four LTBPs isoforms in the human genome (LTBP-1, −2, −3, and −4), all of which appear to associate with fibrillin and the biology of each isoform is reviewed here. The LTBPs were first identified as forming latent complexes with TGFβ by covalently binding the TGFβ propeptide (LAP) via disulfide bonds in the endoplasmic reticulum. LAP in turn is cleaved from the mature TGFβ precursor in the trans-golgi network but LAP and TGFβ remain strongly bound through non-covalent interactions. LAP, TGFβ, and LTBP together form the large latent complex (LLC). LTBPs were originally thought to primarily play a role in maintaining TGFβ latency and targeting the latent growth factor to the extracellular matrix (ECM), but it has also been shown that LTBP-1 participates in TGFβ activation by integrins and may also regulate activation by proteases and other factors. LTBP-3 appears to have a role in skeletal formation including tooth development. As well as having important functions in TGFβ regulation, TGFβ-independent activities have recently been identified for LTBP-2 and LTBP-4 in stabilizing microfibril bundles and regulating elastic fiber assembly. •We describe structures and interactions of the four latent transforming growth factor beta binding proteins (LTBP) proteins.•The biological functions of the four LTBPs