Cellular Factor XIIIA Transglutaminase Localizes in Caveolae and Regulates Caveolin-1 Phosphorylation, Homo-oligomerization and c-Src Signaling in Osteoblasts

Wang, Shuai; Kaartinen, Mari T.

doi:10.1369/0022155415597964

Cited by 4 publications

(2 citation statements)

References 66 publications

(107 reference statements)

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“…39,40 FXIII-A was detected in caveolae within the cell membrane of differentiating osteoblasts and suggested to be involved in the regulation of signaling processes. 41 However, in contrast to the above results, normal bone deposition was recently reported to occur in double knockout mice deficient in both FXIII-A and transglutaminase 2. 42 Human FXIII deficiency is not associated with abnormal bone formation either.…”

Section: Factor XIII In Bone Biologymentioning

confidence: 77%

Factor XIII: Structure and Function

Schroeder

Köhler

2016

Semin Thromb Hemost

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Over the last two decades, it became evident that factor XIII (FXIII) is not only a crucial determinant of clot characteristics but also has potentially important functions in many various fields such as bone biology, immunity, and adipogenesis. In this review, we aim to summarize the latest findings regarding structure and function of FXIII. In regard to FXIII structure, much progress has been made recently to understand how its subunits are held together. In the A subunit, the activation peptide has a crucial role in the formation of FXIII-A2 dimers. In the B subunit, Sushi domains that are involved in binding to the A subunit and in B2 dimer formation have been identified. In regard to FXIII function, interactions with immune cells and the complement system have been described. A novel function of FXIII-A in adipogenesis has been suggested. The role of FXIII-A in osteoblast differentiation has been further investigated; however, a novel double knockout mouse deficient in both FXIII-A and transglutaminase 2 showed normal bone formation. Thus, more research, in particular, into the cellular functions of FXIII-A is still required.

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Section: Factor XIII In Bone Biologymentioning

confidence: 77%

Factor XIII: Structure and Function

Schroeder

Köhler

2016

Semin Thromb Hemost

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“…Calveolae are lipid raft plasma membrane invaginations that are involved in the regulation of endocytosis and intracellular signal transduction, via the clustering of receptors and signaling molecules. In differentiating osteoblasts, FXIII‐A colocalizes intracellularly with caveolin‐1 on the inner leaflet of calveolae, where it is involved in intracellular signaling by regulating interactions between caveolin‐1 and c‐SRC kinase . This regulatory signaling role in osteoblasts suggests that FXIII‐A may also be involved in signaling pathways in other cells.…”

Section: Fxiii‐a In Bonementioning

confidence: 99%

Let's cross‐link: diverse functions of the promiscuous cellular transglutaminase factor XIII‐A

Mitchell

Mutch

2019

Journal of Thrombosis and Haemostasis

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Plasma Factor XIII, a heterodimer of A and B subunits FXIIIA2B2, is a transglutaminase enzyme with a well‐established role in haemostasis. Cells of bone marrow and mesenchymal lineage express the FXIII‐A gene (F13A1) that encodes the cellular form of the transglutaminase, a homodimer of the A subunits, FXIII‐A. FXIII‐A was presumed to function intracellularly, however, several lines of evidence now indicate that FXIII‐A is externalised by an as yet unknown mechanism This review describes the mounting evidence that FXIII‐A is a diverse transglutaminase with many intracellular and extracellular substrates that can participate in an array of biological processes Summary Factor XIII is a tranglutaminase enzyme that catalyzes the formation of ε‐(γ‐glutamyl)lysyl isopeptide bonds in protein substrates. The plasma form, FXIII‐A2B2, has an established function in hemostasis, where its primary substrate is fibrin. A deficiency in FXIII manifests as a severe bleeding diathesis, underscoring its importance in this pathway. The cellular form of the enzyme, a homodimer of the A‐subunits, denoted FXIII‐A, has not been studied in as extensive detail. FXIII‐A was generally perceived to remain intracellular, owing to the lack of a classical signal peptide for its release. In the last decade, emerging evidence has revealed that this diverse transglutaminase can be externalized from cells, by an as yet unknown mechanism, and can cross‐link extracellular substrates and participate in a number of diverse pathways. The FXIII‐A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage, notably megakaryocytes, monocytes/macrophages, dendritic cells, chrondrocytes, osteoblasts, and preadipocytes. The biological processes that FXIII‐A is coupled with, such as wound healing, phagocytosis, and bone and matrix remodeling, reflect its expression in these cell types. This review describes the mounting evidence that this cellular transglutaminase can be externalized, usually in response to stimuli, and participate in extracellular cross‐linking reactions. A corollary of being involved in these biological pathways is the participation of FXIII‐A in pathological processes. In conclusion, the functions of this transglutaminase extend far beyond its role in hemostasis, and our understanding of this enzyme in terms of its secretion, regulation and substrates is in its infancy.

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