Factor XIIIa as a nerve‐associated transglutaminase

Abstract

Recent findings have led to changes in the traditional concept of nerve recovery, including the realization that injured nerves, like any other injured tissue, need the assistance of blood-derived cells and factors in order to heal. We show that factor XIIIa (FXIIIa, the potentially active a2subunit of factor XIII), an enzyme that participates in blood coagulation by stabilizing the fibrin clot, is also active in the nervous system where it may play a key role in the healing of injured tissue. We demonstrate that the plasma, macrophages and nerves of fish contain a 55 kDa form of transglutaminase that cross-reacts immunologically with the a-subunit of FXIII in mammals (80 kDa). The fish enzyme in the plasma, unlike its mammalian counterpart, is active, pointing to a difference in control of the coagulation pathway in the two species. Analysis of FXIIIa expression in mammalian neural tissues and their response to injury revealed high levels of the enzyme in media conditioned by peripheral nerves as compared with medium conditioned by nerves of the central nervous system. Furthermore, similarity was observed in the postinjury behavior of FXIIIa in regenerating nerve tissues (peripheral nervous system of mammals and the central nervous system of fish). We suggest that the postinjury level of factor XIIIa in the nervous system may be related to the tissue's regenerative capacity, and that FXIIIa may therefore be a link underlying a possible association between the processes of blood coagulation and nerve healing.

A distinct effect of transient and sustained upregulation of cellular factor XIII in the goldfish retina and optic nerve on optic nerve regeneration

“…3) matched well with the period of axon elongation . Furthermore, Monsonego et al (1998) reported that crushed fish optic nerves released FXIII exhibiting TG enzymatic activity. Our retinal explant culture experiments clearly showed that FXIII derived from injured optic nerves induced neurite outgrowth from primed retina with optic nerve injury from 3 days beforehand, but not from unprimed (naïve) retina whose optic nerve was transectioned just before removing the eye in order to make the explants (Fig.…”

Chicken Coagulation Factor XIIIA Is Produced by the Theca Externa and Stabilizes the Ovarian Follicular Wall

“…Although the presence of factor XIIIA in these cells has been known for many years, the function of this form is still unclear. Recent reports (13,14,24) suggest that plasma factor XIIIA has specialized functions in certain other tissues and cells independent of its function in the blood. It seems to be associated with peripheral nervous tissue and may play a role in the regeneration of this tissue after injury (24).…”

“…Recent reports (13,14,24) suggest that plasma factor XIIIA has specialized functions in certain other tissues and cells independent of its function in the blood. It seems to be associated with peripheral nervous tissue and may play a role in the regeneration of this tissue after injury (24). These authors present circumstantial evidence that XIIIA is at least partially synthesized by macrophages present in the nervous tissue.…”

Serine 129 Phosphorylation of α-Synuclein Cross-Links with Tissue Transglutaminase to Form Lewy Body-Like Inclusion Bodies

“…It is predominantly expressed in the central nervous system and has functions in neural development, neural regeneration, and others [8, 9]. tTG mediates the posttranslational modification of proteins including the crosslinking and the polypeptide formation.…”