Tissue transglutaminase during mouse central nervous system development: lack of alternative RNA processing and implications for its role(s) in murine models of neurotrauma and neurodegeneration.
Tissue transglutaminase (tTG) is a member of a multigene family principally involved in catalyzing the formation of protein cross-links. Unlike other members of the transglutaminase family, tTG is multifunctional since it also serves as a guanosine triphosphate (GTP) binding protein (Galpha(h)) and participates in cell adhesion. Different isoforms of tTG can be produced by proteolysis or alternative splicing. We find that tTG mRNA is expressed at low levels in the mouse CNS relative to other tissues, and at lower levels in the CNS of mouse in comparison to that of human or rat. tTG mRNA levels are higher in the heart compared to the CNS, for example, and much higher in the liver. Within the CNS, tTG message is lowest in the adult cerebellum and thalamus and highest in the frontal cortex and striatum. In the hippocampus, tTG expression is highest during embryonic development and falls off dramatically after 1 week of life. We did not find alternative splicing of the mouse tTG. At the protein level, the predominant isoform is approximately 62 kDa. In summary, tTG, an important factor in neuronal survival, is expressed at low levels in the mouse CNS and, unlike rat and human tTG, does not appear to be regulated by alternative splicing. These findings have implications for analyses of rodent tTG expression in human neurodegenerative and neurotrauma models where alternative processing may be an attractive pathogenetic mechanism. They further impact on drug discovery paradigms, where modulation of activity may have therapeutic value.
Citron
Bruce A
BA
Molecular Biology, Veterans Affairs Medical Center, 4801 Linwood Boulevard, Kansas City, MO 64128, USA.
Zoloty
Jamie E
JE
Suo
Zhiming
Z
Festoff
Barry W
BW
D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002460:Cell Line; D002490:Central Nervous System / Q000033:anatomy & histology / Q000196:embryology / Q000201:enzymology*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D012333:RNA, Messenger; D014212:Tretinoin; D011503:Transglutaminases