LTBP-2 has multiple heparin/heparan sulfate binding sites

Parsi, Mahroo K.; Adams, Julian; Whitelock, John M.; Gibson, Mark

doi:10.1016/j.matbio.2010.03.005

Cited by 32 publications

(29 citation statements)

References 46 publications

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“…Although no typical heparin-binding consensus sequences are found in EMILIN-3, our data clearly indicate that the EMI domain alone is sufficient to bind heparin. Notably, among the extracellular proteins known to bind heparin/heparan sulfate chains, there are several elastic fiber-associated proteins, such as tropoelastin (35), fibrillin-1 (36), latent TGF-␤ binding proteins (37,38), and various members of the TGF-␤ superfamily (39).…”

Section: Discussionmentioning

confidence: 99%

EMILIN-3, Peculiar Member of Elastin Microfibril Interface-located Protein (EMILIN) Family, Has Distinct Expression Pattern, Forms Oligomeric Assemblies, and Serves as Transforming Growth Factor β (TGF-β) Antagonist

Schiavinato

Becker

Zanetti

et al. 2012

Journal of Biological Chemistry

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Background: EMILIN-3 is the least characterized member of the EMILIN/Multimerin family. Results: EMILIN-3 forms homotrimers and higher order oligomers, binds heparin, has a dynamic expression during development and a restricted distribution in adult tissues, and serves as a pro-TGF-␤ antagonist. Conclusion:The structure and expression of EMILIN-3 are different from other EMILINs/Multimerins. Significance: EMILIN-3, a TGF-␤ antagonist, is likely to be an important regulator during development of several tissues.

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Section: Discussionmentioning

confidence: 99%

EMILIN-3, Peculiar Member of Elastin Microfibril Interface-located Protein (EMILIN) Family, Has Distinct Expression Pattern, Forms Oligomeric Assemblies, and Serves as Transforming Growth Factor β (TGF-β) Antagonist

Schiavinato

Becker

Zanetti

et al. 2012

Journal of Biological Chemistry

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“…It has been previously demonstrated that fibulin-4 and -5 are in charge of recruiting tropoelastins and its cross-linking enzymes onto microfibrils in order to accelerate elastic fiber assembly in collaboration with LTBP-2, which binds to heparin and heparin sulfate proteoglycans4546474849. In addition, the abundance of fibulin-5 has also been documented to be decreased both in photoaged and in intrinsically aged dermis, suggesting that it plays a role in maintaining cutaneous elasticity50.…”

Section: Discussionmentioning

confidence: 99%

Essential role of microfibrillar-associated protein 4 in human cutaneous homeostasis and in its photoprotection

Kasamatsu

Hachiya

Fujimura

et al. 2011

Sci Rep

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UVB-induced cutaneous photodamage/photoaging is characterized by qualitative and quantitative deterioration in dermal extracellular matrix (ECM) components such as collagen and elastic fibers. Disappearance of microfibrillar-associated protein 4 (MFAP-4), a possible limiting factor for cutaneous elasticity, was documented in photoaged dermis, but its function is poorly understood. To characterize its possible contribution to photoprotection, MFAP-4 expression was either augmented or inhibited in a human skin xenograft photodamage murine model and human fibroblasts. Xenografted skin with enhanced MFAP-4 expression was protected from UVB-induced photodamage/photoaging accompanied by the prevention of ECM degradation and aggravated elasticity. Additionally, remarkably increased or decreased fibrillin-1-based microfibril development was observed when fibroblasts were treated with recombinant MFAP-4 or with MFAP-4-specific siRNA, respectively. Immunoprecipitation analysis confirmed direct interaction between MFAP-4 and fibrillin-1. Taken together, our findings reveal the essential role of MFAP-4 in photoprotection and offer new therapeutic opportunities to prevent skin-associated pathologies.

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“…LTBP-2 binds to heparin and heparan sulfate proteoglycans through its N-terminus and, more weakly, through the central EGF repeat-rich region (Parsi et al 2010). This interaction might help provide additional anchoring of microfibrils to basal membranes.…”

Section: Ltbp-2mentioning

confidence: 99%

Latent TGF-β-binding proteins

et al. 2015

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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.

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LTBP-2 has multiple heparin/heparan sulfate binding sites

Cited by 32 publications

References 46 publications

EMILIN-3, Peculiar Member of Elastin Microfibril Interface-located Protein (EMILIN) Family, Has Distinct Expression Pattern, Forms Oligomeric Assemblies, and Serves as Transforming Growth Factor β (TGF-β) Antagonist

EMILIN-3, Peculiar Member of Elastin Microfibril Interface-located Protein (EMILIN) Family, Has Distinct Expression Pattern, Forms Oligomeric Assemblies, and Serves as Transforming Growth Factor β (TGF-β) Antagonist

Essential role of microfibrillar-associated protein 4 in human cutaneous homeostasis and in its photoprotection

Latent TGF-β-binding proteins

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