A cell-cycle–dependent GARP-like transcriptional repressor regulates the initiation of differentiation in Giardia lamblia

Abstract

Significance Transition between life cycle stages is a common feature among parasitic pathogens, and its regulation must be optimized to balance persistence of infection with transmission. The early transcription factors (TFs) regulating commitment to differentiate are totally unknown in Giardia . In this work, we identified Golden2, ARR-B, Psr-1–like protein 1 (GARP)–like protein 4 (GLP4), a previously uncharacterized GARP-like TF, as an early-acting transcriptional repressor that inhibits G1+S cells from entering the encystation pathway. GLP4 is therefore a key regulator controlling the balance between proliferative growth and terminal differentiation into infective cysts.

Encystation stimuli sensing mediated by adenylate cyclase AC2-dependent cAMP signaling inGiardia

“…We next questioned whether the reduction in cAMP and PKAc activation would alter the encystation response. Since Myb2, has been shown to regulate CWP1, CWP2, CWP3, and GalNAc synthesis enzymes and is necessary for cyst formation 23 , we used this important protein as a readout for encystation. We transformed the dCas9-Ctrl and AC2-g4159 knockdown constructs into MYB2-NLuc and CWP1-NLuc cell lines respectively so that their expression could be monitored.…”