SCE1

SCE1 (Suppressor of Ca2+-dependent Egress 1) is a negative regulator of rapid Ca2+-dependent host cell egress in Toxoplasma gondii, acting downstream of the calcium-dependent protein kinase CDPK3 (PMID:28258212). It was identified in a forward genetic screen in which gain-of-function mutations in SCE1 restored egress in a Δcdpk3 background, genetically placing SCE1 within the Ca2+ signaling pathway that controls egress (PMID:28258212). CDPK3-dependent phosphorylation of SCE1 relieves its suppressive activity, and deletion of SCE1 restores many Δcdpk3-dependent phosphorylation events toward wild-type levels, establishing SCE1 as the physiological brake on egress that CDPK3 antagonizes (PMID:28258212). Beyond this genetic and phosphoproteomic placement, no biochemical mechanism, direct substrates, or structural detail for SCE1 has been characterized in the available corpus.

1. 2017 Medium

   Identifying a downstream effector of CDPK3 in egress signaling: SCE1 was found as a negative regulator whose gain-of-function mutations bypass the loss of CDPK3, defining a genetic brake on Ca2+-dependent egress.

   Evidence Forward genetic screen for gain-of-function suppressors in a Δcdpk3 background with genetic epistasis, in Toxoplasma gondii

   PMID:28258212

   Open questions at the time

   • The molecular identity of the process SCE1 suppresses (e.g. direct effectors) is not defined
   • Whether SCE1 acts on egress machinery directly or through intermediaries is unknown
   • No biochemical or structural characterization of SCE1
2. 2017 Medium

   Establishing the regulatory logic: CDPK3-dependent phosphorylation of SCE1 relieves its suppression, since SCE1 deletion restores Δcdpk3-dependent phosphorylation events, positioning SCE1 as the target through which CDPK3 potentiates egress.

   Evidence Global phosphoproteomic analysis combined with genetic deletion of SCE1 in a Δcdpk3 background, in Toxoplasma gondii

   PMID:28258212

   Open questions at the time

   • Direct phosphorylation of SCE1 by CDPK3 not demonstrated in vitro
   • The specific phosphosites and their functional consequences are not mapped
   • Downstream substrates whose phosphorylation SCE1 controls are unidentified

• The biochemical activity of SCE1, its direct interaction partners, and the molecular mechanism by which it suppresses Ca2+-dependent egress remain undefined.
• No molecular function or enzymatic activity assigned to SCE1
• No subcellular localization established
• No structural model or direct binding partners identified