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Published on: February 20, 2020
Structurally distinct genes for the surface protease of Leishmania mexicana are developmentally regulated
E Medina-Acosta1, R E Karess, D G Russell
1Department of Pathology, New York University Medical Center, NY.
Abstract:
gp63 is a highly abundant glycosylphosphatidylinositol (GPI)-anchored membrane protein expressed in both the promastigote and the amastigote forms of Leishmania species. In Leishmania mexicana, gp63 exists as a heterogeneous family of proteins that are differentially processed and localized during the 2 developmental stages. In this study we determined the molecular organization of the L. mexicana gp63 gene family, demonstrating that the gp63 genes fall into 3 linked families of tandemly repeated, but structurally distinct, entities designated as C1, C2 and C3. The C1 and C2 gene clusters contain 4-5 copies each, while the C3 gene may be single copy. Whilst promastigotes contain transcripts from all 3 gene classes, the intracellular amastigote only expresses detectable transcript from the C1 gene class. Moreover, the sequence of the C1 genes predicts a unique carboxy terminus substantially different from the GPI anchor addition signal sequence found in other Leishmania spp. and which has characteristics incompatible with substitution with a GPI anchor. These findings have significance for both the diversity of gp63 and for the regulation of tightly clustered, tandem gene arrays.
Insights
Leishmania mexicana gp63 genes are organized into three distinct families (C1, C2, C3). Only C1 gene transcripts are detected in amastigotes, suggesting stage-specific gene regulation for this abundant surface protein.
Area of Science:
- Molecular biology
- Parasitology
- Genetics
Background:
- gp63 is a key glycosylphosphatidylinositol (GPI)-anchored membrane protein in Leishmania species.
- gp63 exhibits heterogeneity and differential processing across developmental stages in Leishmania mexicana.
Purpose of the Study:
- To elucidate the molecular organization of the Leishmania mexicana gp63 gene family.
- To investigate the differential expression of gp63 gene classes during parasite development.
Main Methods:
- Analysis of the molecular organization of gp63 gene clusters.
- Transcriptional analysis across different Leishmania developmental stages.
Main Results:
- gp63 genes in L. mexicana are organized into three distinct, tandemly repeated gene families: C1, C2, and C3.
- Promastigotes express transcripts from all three gene classes (C1, C2, C3).
- Intracellular amastigotes predominantly express transcripts from the C1 gene class, which has a unique C-terminal sequence potentially incompatible with GPI anchoring.
Conclusions:
- The findings reveal significant diversity within the L. mexicana gp63 gene family.
- Differential expression of gp63 gene classes suggests stage-specific regulation impacting protein function and localization.
- The unique C1 gene sequence has implications for GPI anchor addition and parasite biology.
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