identifier: traitmech:000634
label: macropinocytosis
definition: A physiological phenotype in which a microbial organism internalizes bulk
  extracellular fluid by closing actin-driven plasma-membrane ruffles into large intracellular
  vesicles.
definition_source: DOI:10.1242/jcs.213736
trait_category: PHYSIOLOGY
term_kind: CLASS
mapping_status: PROPOSED
parent_traits:
- traitmech:000635
evidence:
- reference: DOI:10.1242/jcs.213736
  snippet: Macropinocytosis is a conserved endocytic process used by Dictyostelium
    amoebae for feeding on liquid medium.
  notes: PMID:29440238, PMC5897714. Scientific ABSTRACT quote. Introduction supports
    the ruffle-closure definition. Relevant uptake Results, Methods, Discussion and
    actual Figure 2 were read at https://pmc.ncbi.nlm.nih.gov/articles/PMC5897714/.
    Figure 2E reports P=0.057 for DdB formation-rate upregulation; do not call this
    significant. Diameter measurements use a transgenic reporter, unlike the dextran
    formation assay. Other figures and supplements were not visually audited.
- reference: DOI:10.7554/eLife.04940
  snippet: These cells can also internalise bulk fluid without the guidance of a particle
    using a closely related process, macropinocytosis
  notes: PMID:25815683, PMC4374526. Contiguous Introduction quote, not the scientific
    Abstract or eLife digest. Relevant Results, confocal Methods, Discussion, Table
    2 and actual Figure 3 were read at https://pmc.ncbi.nlm.nih.gov/articles/PMC4374526/.
    Figure 3C measures formation events; Figure 3B single sections cannot quantify
    cumulative uptake. Other figures and movies were not visually audited.
canonical_examples:
- taxon_id: NCBITaxon:44689
  taxon_label: Dictyostelium discoideum
  reference: DOI:10.7554/eLife.04940
  note: Wild-type parental DdB cells freshly harvested from bacterial growth, observed
    by dextran imaging in Figure 3C; not Ax2, AX4, NF1 knockouts or reporter transformants.
    Table 2 links DdB to DdB(Wel). Strain genealogy at https://link.springer.com/article/10.1186/gb-2008-9-4-r75
    identifies a laboratory-selected NC4 clone with copy-number differences, not an
    unchanged original wild isolate. NCBI EFetch verified the name and species rank
    on 2026-10-06; this ID does not identify the strain.
discussions:
- discussion_id: macropinocytosis-scope-and-hierarchy
  prompt: Keep bulk-fluid uptake distinct from neighboring uptake traits.
  kind: CURATION_TODO
  status: RESOLVED
  rationale: Retain phenotype METPO:1000059 pending a closer endocytic capability
    hierarchy. This is uptake by a microbe, not microbial induction of uptake by a
    host cell. Phagocytosis traitmech:000627 is particle engulfment, phagotrophy traitmech:000628
    requires nutritional assimilation, and trogocytosis traitmech:000633 removes portions
    of living cells. These are neither equivalents nor disjoint organismal capabilities.
    Generic pinocytosis is broader; its existing phagocytosis discussion mention is
    not an exact unresolved macropinocytosis node. Membrane ruffling without closure,
    solute transport alone and uptake into small endocytic vesicles are insufficient.
    No fixed diameter cutoff, enhanced uptake rate, axenic growth or nutrition is
    required. No unverified synonym or process-level ontology xref is asserted.
  posed_by: codex
  posed_date: '2026-10-06'
  resolved_date: '2026-10-06'
  resolution_note: Added pinocytosis traitmech:000635 as the direct broader phenotype.
    The existing ruffle-mediated bulk-fluid definition entails vesicular fluid uptake;
    its definition, evidence and DdB example are unchanged. This resolves the temporary
    phenotype-parent gap, not the separate native-mechanism discussion or any ontology
    equivalence. Preserve the historical v510 phenotype axiom and add METPO:1058700
    SubClassOf METPO:1058800 on upstream adoption.
- discussion_id: macropinocytosis-native-mechanism
  prompt: Separate native capability from mutant and reporter mechanisms.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: The papers share a research group and organism; they are not independent
    taxon replication. NF1 loss enhances uptake but is not required for the phenotype.
    Do not equate a drug response, localization or sequence similarity with a universal
    causal dependency. Protein accessions, native functional scope and remaining figures
    require review before adding protein examples or a causal graph.
  posed_by: codex
  posed_date: '2026-10-06'
curation_history:
- timestamp: '2026-10-06T04:39:00Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Added macropinocytosis with two DOI-backed source snippets and a parental
    DdB-qualified example. Ignored-and-hidden searches and pinned METPO review found
    no exact record. Reserved METPO:1058700 in v510. Distinguished native uptake from
    axenic mutants, reporter measurements and universal mechanisms.
  llm_assisted: true
- timestamp: '2026-10-06T05:29:34Z'
  curator: codex
  action: REFINE_PINOCYTOSIS_PARENT
  changes: Refined the direct parent to pinocytosis traitmech:000635 and resolved
    the temporary hierarchy discussion by definition-based inference. Preserved identity,
    definition, evidence, canonical example, mechanism gap, earlier history and the
    true broader historical proposal axiom.
  llm_assisted: true