AFRICAN TRYPANOSOMES HAVE DIFFERENTIALLY EXPRESSED GENES ENCODING HOMOLOGS OF THE LEISHMANIA GP63 SURFACE PROTEASE

The genomes of various Leishmania parasites contain tandemly arrayed g enes encoding an abundant; 63-kDa surface glycoprotein called GP63. Le ishmania GP63s are metalloproteases that play an important role in the invasion and survival of the parasites within the macro phage, and th eir presence on the Leishmania surface has been correlated with resist ance to complement;mediated lysis, Here we report the identification o f GP63-like genes in African trypanosomes. The predicted trypanosome a nd Leishmania GP63s share a metalloprotease catalytic site motif of HE XXH as well as 19 cysteines and 10 prolines, implying a conservation o f enzymatic activity and secondary/tertiary structure. The trypanosome GP63 genes are. transcribed equally in procyclic and bloodstream tryp anosomes, but their mRNAs accumulate to a 50-fold higher steady state level in bloodstream trypanosomes, where the ratio of mRNAs for GP63 a nd variant surface glycoprotein is about 1:150. Transcription of the G P63 genes is sensitive to alpha-amanitin, indicating that they are tra nscribed by a different polymerase than the variant, surface glycoprot ein genes, These results lead to a reconsideration of the potential fu nctions of GP63, inasmuch as African trypanosomes are not known to int eract with macrophages and do not have an intracellular stage during t heir life cycle.