TRAPPC14

TRAPPC14 (C7orf43/MAP11) is a TRAPPII-specific complex subunit that functions at the intersection of ciliogenesis and mitotic cell division. It co-sediments with TRAPPII subunits and, while dispensable for overall complex integrity, directly binds Rabin8 and mediates its association with the TRAPPII complex, thereby driving Rabin8 preciliary centrosomal accumulation required for ciliogenesis; it also interacts with the distal appendage proteins FBF1 and CEP83, supporting a vesicle-tethering role at the mother centriole (PMID:31467083). In mitosis, TRAPPC14 associates with α-tubulin on the mitotic spindle and co-localizes with PLK1 at the midbody during cytokinetic abscission, and its silencing reduces neuronal cell proliferation without affecting apoptosis (PMID:30715179). Loss of TRAPPC14 function causes ciliogenesis defects in both human cells and zebrafish embryos (PMID:31467083).

1. 2019 High

   Establishing TRAPPC14 as a TRAPPII-specific subunit and Rabin8 effector resolved how the TRAPPII complex recruits Rabin8 to the centrosome during early ciliogenesis — a previously undefined targeting mechanism.

   Evidence MS-based interactome, co-sedimentation with TRAPPII subunits, direct binding assays, and siRNA knockdown with centrosomal Rabin8 accumulation readout in human cells

   PMID:31467083

   Open questions at the time

   • Structural basis of the TRAPPC14–Rabin8 interaction is unknown
   • Whether TRAPPC14 contributes to TRAPPII GEF activation of Rab11 is untested
   • Temporal regulation of TRAPPC14 incorporation into TRAPPII is not defined
2. 2019 Medium

   Demonstration that TRAPPC14 interacts with distal appendage proteins FBF1 and CEP83 provided a physical link between the TRAPPII vesicle-trafficking complex and the centriolar docking machinery, explaining how preciliary vesicles are tethered to the mother centriole.

   Evidence Co-immunoprecipitation of TRAPPC14 with FBF1 and CEP83; knockdown of these DAPs phenocopied loss of centrosomal Rabin8

   PMID:31467083

   Open questions at the time

   • Interactions with FBF1 and CEP83 rely on Co-IP without reciprocal validation or domain mapping
   • Whether TRAPPC14 directly contacts distal appendage proteins or bridges through other TRAPPII subunits is unresolved
3. 2019 Medium

   Parallel work revealed a distinct mitotic function: TRAPPC14 associates with α-tubulin on the spindle and with PLK1 at the midbody, and its depletion reduces neuronal cell proliferation, establishing a dual role in both ciliogenesis and cell division.

   Evidence Immunofluorescence and Co-IP in SH-SY5Y cells; lentiviral shRNA knockdown with proliferation versus apoptosis discrimination; CRISPR knockout in zebrafish

   PMID:30715179

   Open questions at the time

   • Whether TRAPPC14 functions at the spindle as part of the TRAPPII complex or independently is unknown
   • The mechanism by which TRAPPC14 regulates abscission timing is not defined
   • Causal link between midbody function and the microcephaly phenotype awaits direct demonstration
4. 2019 Low

   An shRNA screen identified a role for TRAPPC14 in upregulating TERT expression through YAP1, suggesting a potential link to telomerase regulation in cancer cells.

   Evidence Genome-wide shRNA screen and promoter-reporter assays in cancer cell lines

   PMID:30447097

   Open questions at the time

   • Single-lab finding without independent replication or detailed mechanistic follow-up on the YAP1 connection
   • Relationship between TERT regulation and known TRAPPII/ciliogenesis functions is unexplored

• Key open questions include whether TRAPPC14's spindle and ciliogenesis functions represent independent or coordinated activities, the structural basis of its interactions, and whether loss-of-function mutations cause human ciliopathy or microcephaly.
• No human genetic disease formally linked via causative mutation in the available timeline evidence
• No structural or cryo-EM data on TRAPPC14 within the TRAPPII complex
• Whether ciliogenesis and mitotic roles are cell-type or cell-cycle dependent is unresolved