CAM2

CAM2 is a calmodulin-like protein of Toxoplasma gondii that supports the apical motility machinery driving parasite gliding, host-cell invasion, and egress (PMID:28475612). It localizes to the conoid at the parasite's apical tip, where it overlaps with the conoid myosin MyoH (PMID:28475612). CAM2 functions redundantly with CaM1: either protein is individually dispensable, but their combined loss is synthetically lethal, establishing overlapping roles among the conoid calmodulin-like proteins (PMID:28475612). Functionally, CAM2 acts downstream of microneme and rhoptry secretion in the invasion/egress program (PMID:28475612). Proximity biotinylation places CAM2 near MyoH and its light chain MLC7, and disruption of MyoH causes CAM2 to redistribute, consistent with a functional association with the conoid myosin motor (PMID:28475612). Beyond these findings, no further biochemical or structural detail of CAM2 has been characterized in the available corpus.

1. 2017 High

   Whether the conoid calmodulin-like proteins had non-overlapping essential roles was unknown; genetic epistasis established that CaM1 and CAM2 are functionally redundant, each dispensable alone but jointly essential.

   Evidence CRISPR/Cas9 double-knockout epistasis in T. gondii

   PMID:28475612

   Open questions at the time

   • Does not resolve which molecular functions are shared versus unique between CaM1 and CAM2
   • Molecular basis of the redundancy (shared partners, shared calcium targets) not defined
2. 2017 High

   The subcellular site of action was unknown; super-resolution imaging placed CAM2 at the apical conoid overlapping MyoH, defining where it operates within the invasion machinery.

   Evidence Super-resolution microscopy of tagged CAM2 in T. gondii

   PMID:28475612

   Open questions at the time

   • Does not establish direct binding to any conoid protein
   • Spatial overlap with MyoH does not prove physical interaction
3. 2017 Medium

   The cellular process CAM2 supports was unclear; conditional degradation showed it contributes to motility, invasion, and egress acting downstream of microneme and rhoptry secretion.

   Evidence Auxin-induced degron depletion with motility/invasion/egress assays in T. gondii

   PMID:28475612

   Open questions at the time

   • CAM2's individual contribution is inferred partly from redundancy and combined-knockdown data
   • The specific step in the motility cascade CAM2 controls is not resolved
4. 2017 Medium

   Whether CAM2 physically partners with the conoid motor was unknown; proximity biotinylation labeled MyoH and MLC7, and MyoH disruption redistributed CAM2, indicating a functional association with the myosin motor.

   Evidence BioID proximity biotinylation plus MyoH disruption with imaging readout in T. gondii

   PMID:28475612

   Open questions at the time

   • Interaction inferred from proximity labeling and epistasis, not confirmed by reciprocal Co-IP or pull-down
   • Whether CAM2 binds MyoH directly or via MLC7/other bridging proteins is undefined
   • No structural or stoichiometric characterization of a CAM2-MyoH complex

• How CAM2's calmodulin-like activity is regulated (e.g. calcium binding) and its direct molecular targets at the conoid remain unresolved.
• No demonstration of calcium binding or calcium-dependent target engagement for CAM2
• No direct binding partner confirmed biochemically
• No structural model of CAM2 or its complexes