Transgenic Overexpression Of Heat Shock Protein (hsp83) Enhances Protein Kinase A Activity, Disrupts Gp63 Surface Protease Expression And Alters Promastigote Morphology In Leishmania Amazonensis
Molecular and Biochemical Parasitology
Leishmania parasites undergo morphological changes during their infectious life cycle, including developmental transitions within the sandfly vector, culminating in metacyclic stages that are pre-adapted for infection. Upon entering vertebrate host phagocytes, Leishmania differentiate into intracellular amastigotes, the form that is ultimately transmitted back to the vector to complete the life cycle. Although environmental conditions that induce these cellular transitions are well-established, molecular mechanisms governing Leishmania morphologic differentiation in response to these cues remain largely uncharacterized. Previous studies indicate a key role for HSP83 in both promastigote metacyclogenesis and amastigote differentiation. To further elucidate HSP83 functions in the Leishmania lifecycle, we examined the biological impact of experimentally elevating HSP83 gene expression in Leishmania. Significantly, HSP83 overexpression was associated with altered metacyclic morphology, increased protein kinase A (PKA) activity and decreased expression of the Leishmania major surface protease, GP63. Corroborating these findings, overexpression of the L. amazonensis PKA catalytic subunit resulted in a largely similar phenotype. Our findings demonstrate for the first time in Leishmania, a functional link between HSP83 and PKA in the control of Leishmania gene expression, replication and morphogenesis.
Nation, Catherine S.; Stephany-Brassesco, Isabel; Kelly, Ben L.; and Pizarro, Juan C., "Transgenic Overexpression Of Heat Shock Protein (hsp83) Enhances Protein Kinase A Activity, Disrupts Gp63 Surface Protease Expression And Alters Promastigote Morphology In Leishmania Amazonensis" (2023). School of Graduate Studies Faculty Publications. 73.