Regulation of the dual function tissue transglutaminase/G alpha(h) during murine neuromuscular development: gene and enzyme isoform expression

Coagulation Factor XIII (F. VIII), a member of the transglutaminase (TGase) superfamily, is activated by thrombin, crosslinks fibrin and stabilizes cl ots. Another member of this family, tissue TGase (tTG), having similar enzy matic activity, is implicated in neural development and synapse stabilizati on. Our previous studies indicated that synapse formation and maintenance a t the neuromuscular junction (NMJ) involved components of the coagulation c ascade in development. Others then showed that either F. XIII or tTG were l ocalized at NMJs in a developmentally-regulated fashion. In the current stu dies, we addressed the temporal course of skeletal muscle tTG gene expressi on and found maximal expression at birth and continuing into the immediate postnatal period. Subcellular fractionation revealed a relatively constant particulate isoform of TGase activity which predominated in early embryonic muscle development. In contrast, cytosolic TGase specific activity became the major isoform in the postnatal period. The timing of muscle TGase activ ity correlated well with expression of tTG mRNA and we now present novel da ta of Tgm 2 gene expression for tTG in skeletal muscle. Confirming and exte nding the previous studies, TGase becomes localized at NMJs in the early, f urther ramifying in the late, neonatal period. These data suggest that the early pulse of particulate activity could coincide with the period of myobl ast cell death in embryonic muscle. On the other hand, the peak cytosolic T Gase activity occurs in the neonatal period, correlating temporally with mu scle prothrombin expression during activity-dependent synapse elimination a nd possibly the source of the enzyme localized to the NMJ extracellular mat rix resulting in synaptic stabilization. Published by Elsevier Science Ltd.