IAP1

IAP1 (IMC-associated protein 1) is an inner membrane complex-associated protein of Toxoplasma gondii that serves as the key determinant restricting myosin C (MyoC) to the parasite's posterior pole, acting as a central structural component of the MyoC-glideosome alongside GAP80, GAP50, GAP40, and light chains shared with MyoA (PMID:25393004). Its membrane association is conferred by palmitoylation catalyzed by the acyltransferase TgDHHC2 (but not TgDHHC14), and depletion of TgDHHC2 abolishes IAP1 membrane targeting, identifying IAP1 as a likely TgDHHC2 substrate (PMID:32329212). Beyond these two findings, no further mechanistic detail on IAP1 has been characterized in the available corpus.

1. 2014 Medium

   It was unknown what confined MyoC to the parasite posterior; genetic dissection established IAP1 as the determinant of restricted MyoC localization and a core component of the distinct MyoC-glideosome.

   Evidence Genetic deletion of glideosome components with localization and invasion assays in T. gondii

   PMID:25393004

   Open questions at the time

   • Molecular mechanism by which IAP1 anchors or restricts MyoC is not defined
   • Direct physical interaction between IAP1 and MyoC not biochemically resolved
   • Contribution of IAP1 to parasite motility or fitness beyond localization not quantified
2. 2020 Medium

   How IAP1 achieves membrane association was unresolved; conditional depletion showed its membrane targeting requires palmitoylation by TgDHHC2, placing IAP1 downstream of a specific acyltransferase.

   Evidence Conditional knockdown of TgDHHC2 and TgDHHC14 with fluorescence localization of TgIAP1 in T. gondii

   PMID:32329212

   Open questions at the time

   • Direct palmitoylation of IAP1 by TgDHHC2 not shown biochemically (identified as likely substrate via depletion)
   • Palmitoylation site(s) on IAP1 not mapped
   • Whether loss of IAP1 palmitoylation disrupts MyoC-glideosome assembly not tested

• Whether IAP1 directly binds MyoC and how its palmitoylation-dependent membrane anchoring couples to MyoC restriction remains unresolved.
• No structural or direct binding data for the IAP1-MyoC interaction
• Causal link between TgDHHC2-dependent membrane targeting and MyoC posterior restriction untested