GAPM1

GAPM1 (PF3D7_1323700) is a six-pass transmembrane protein of the inner membrane complex (IMC) in Plasmodium falciparum that couples the alveolin cytoskeleton to the actin-myosin glideosome motor and maintains subpellicular structural integrity (PMID:19561073, PMID:34324609). Biochemically it forms highly SDS-resistant oligomeric complexes and co-purifies with alveolin cytoskeletal proteins and, more weakly, with the actin-myosin motor, consistent with a role anchoring the motor to the pellicular cytoskeleton (PMID:19561073). Rather than being a canonical glideosome subunit, GAPM1 is a component of a distinct PhIL1-associated sub-complex within the IMC (PMID:29138437), and its correct IMC localization and steady-state abundance depend on the integrity of this PHIL1 complex scaffold, as shown in P. berghei where knockdown of IMC1g mislocalizes and destabilizes GAPM1 (PMID:39576115). Functionally, depletion of GAPM1 in P. falciparum causes depolymerization of subpellicular microtubules and loss of parasite shape, establishing a direct requirement for GAPM1 in cytoskeletal architecture (PMID:34324609). Beyond these findings, no catalytic activity or direct molecular mechanism of membrane–cytoskeleton coupling for GAPM1 has been characterized in the available corpus.

1. 2009 High

   Before this work it was unclear how the glideosome motor is anchored to the pellicle; identifying GAPM1 as a multi-pass IMC membrane protein that co-purifies with alveolins and the motor established it as a candidate membrane-cytoskeleton link.

   Evidence Subcellular fractionation, detergent-resistance assays, co-IP and fluorescence localization in P. falciparum

   PMID:19561073

   Open questions at the time

   • Direct binding interface between GAPM1 and alveolins or motor components not defined
   • Functional consequence of disrupting GAPM1 not tested in this study
   • Stoichiometry and composition of the SDS-resistant oligomer unresolved
2. 2017 Medium

   It was unknown whether GAPM1 belongs to the canonical glideosome or a separate assembly; co-IP placed it in a distinct PhIL1-associated complex, refining its molecular context.

   Evidence Co-immunoprecipitation / interactome analysis in P. falciparum and P. berghei

   PMID:29138437

   Open questions at the time

   • Single co-IP approach without reciprocal validation for GAPM1 specifically
   • Whether the PhIL1 interaction is direct or bridged is not established
3. 2018 Low

   A test of whether GAPM1 associates with the motor under standard conditions returned a negative result, clarifying that its extreme detergent-resistance, rather than absence of association, limits its recovery in motor pulldowns.

   Evidence MyoA-GFP co-IP followed by LC-MS/MS in P. falciparum 3D7 schizonts

   PMID:28893907

   Open questions at the time

   • Negative result attributed to biochemical properties rather than directly demonstrated
   • Does not resolve whether GAPM1 physically contacts MyoA at all
   • Contrasts with sibling GAPM2/GAPM3 co-purification, leaving GAPM1's motor coupling unclear
4. 2021 Medium

   The cellular function of GAPM1 was untested until conditional depletion showed subpellicular microtubule depolymerization and shape loss, establishing a direct requirement in maintaining cytoskeletal architecture.

   Evidence Conditional knockdown with morphological/ultrastructural readout in P. falciparum

   PMID:34324609

   Open questions at the time

   • Molecular mechanism linking GAPM1 loss to microtubule depolymerization unknown
   • Whether the defect is direct or secondary to IMC disassembly not resolved
   • Reported in a single study
5. 2023 Low

   Whether GAPM1 associates with other pellicle regulatory machinery was addressed by finding it among proteins co-purifying with the SCFFBXO1 ubiquitin ligase at the ookinete pellicle, extending its interaction context.

   Evidence FBXO1-HA co-IP with mass spectrometry in P. berghei ookinetes

   PMID:36898988

   Open questions at the time

   • Single co-IP/MS identifying GAPM1 as one of many co-purifying proteins with no GAPM1-specific follow-up
   • Functional significance of any GAPM1–SCFFBXO1 link untested
   • Whether GAPM1 is a ubiquitylation substrate unknown
6. 2024 Medium

   The hierarchy governing GAPM1 positioning was unresolved; depleting the upstream PHIL1-complex component IMC1g mislocalized and reduced GAPM1, showing GAPM1's IMC localization and abundance depend on the complex scaffold.

   Evidence Conditional knockdown of IMC1g with IFA and immunoblot readout for GAPM1 in P. berghei

   PMID:39576115

   Open questions at the time

   • Whether the effect on GAPM1 is direct or through general IMC destabilization not distinguished
   • Reciprocal dependence of IMC1g on GAPM1 not tested
   • Single-lab result
7. 2026 Low

   The timing and site of GAPM1 incorporation into the IMC was addressed by imaging its colocalization with a lipid transfer protein at the nascent IMC ring, positioning GAPM1 at early IMC membrane assembly adjacent to the centriolar plaque.

   Evidence U-ExM colocalization of GAPM1-smV5 with mCherry-VAB domain of PfVPS13L1 in P. falciparum schizonts

   PMID:41904125

   Open questions at the time

   • Single colocalization experiment with no functional manipulation of GAPM1
   • GAPM1 used as an IMC marker rather than the subject of study
   • No evidence GAPM1 participates in the lipid transfer itself

• The molecular basis by which GAPM1 physically couples the IMC membrane to the alveolin/microtubule cytoskeleton and how its loss triggers microtubule depolymerization remain undefined.
• No direct binding interface or structural model for GAPM1
• Mechanism connecting GAPM1 to subpellicular microtubule stability unknown
• No reconstitution of the SDS-resistant GAPM1 oligomer