CCDC120

CCDC120 is a multi-compartment coiled-coil scaffold protein that organizes microtubule-anchoring and junctional machinery across distinct cellular contexts (PMID:28422092, PMID:25326380, PMID:42098154). At the centriole subdistal appendages it is anchored by ODF2 and uses distinct N-terminal coiled-coil domains to hierarchically recruit CEP170 and Ninein, an activity required for centrosomal microtubule anchoring in interphase cells; its recruitment of CEP170 is antagonized by CCDC68, which competes for the same interaction (PMID:28422092). CCDC120 serves as the centrosomal targeting mediator for CEP170, whose C-terminal truncations lose centrosomal and microtubule localization when the CCDC120 interaction is disrupted (PMID:41888776). In neurons, the CC1 coiled-coil domain binds cytohesin-2, an Arf6 guanine-nucleotide exchange factor, and directs its anterograde vesicular transport into growing neurites; loss of CCDC120 disperses cytohesin-2, reduces Arf6 activation, and inhibits neurite growth (PMID:25326380). At cardiac desmosomes CCDC120 undergoes liquid-liquid phase separation and co-condenses with plakophilin-2 to preserve desmosomal and intercalated disc integrity, a behavior tuned by PKCα-mediated phosphorylation; its loss causes cardiac dysfunction in mice (PMID:42098154).

1. 2014 High

   Established the first molecular function for CCDC120 by showing its CC1 domain couples the Arf6-GEF cytohesin-2 to vesicular transport driving neurite outgrowth, defining it as a transport scaffold rather than an inert structural protein.

   Evidence Co-IP, domain-deletion rescue, live-cell vesicle imaging, and Arf6 GGA-pulldown activation assay in N1E-115 neuronal cells

   PMID:25326380

   Open questions at the time

   • Structural basis of the CC1-cytohesin-2 interaction unresolved
   • Whether the same domain mediates the centriolar functions later described was not tested
   • Identity of the motor/vesicle machinery transporting the complex not defined
2. 2017 High

   Defined CCDC120 as a subdistal appendage component that uses ODF2 for anchoring and separate N-terminal coiled-coil domains to recruit CEP170 and Ninein, placing it within a hierarchical microtubule-anchoring module subject to CCDC68 competition.

   Evidence siRNA knockdown, reciprocal co-IP, domain-mapping deletion constructs, and immunofluorescence in human cells

   PMID:28422092

   Open questions at the time

   • Structural architecture of the SDA scaffold not resolved
   • Regulation of the CCDC120/CCDC68 competition not defined
   • Relationship between centriolar and neuronal functions unaddressed
3. 2026 High

   Extended CCDC120 into a third compartment, showing it phase-separates and co-condenses with plakophilin-2 under PKCα control to maintain desmosomal/intercalated-disc integrity, with knockout causing cardiac dysfunction in vivo.

   Evidence Live-cell LLPS imaging, PKP2 co-condensation assays, PKCα phosphorylation assays, and CCDC120 knockout mice with cardiac phenotyping

   PMID:42098154

   Open questions at the time

   • Phosphosites controlling condensate behavior not mapped
   • Whether desmosomal LLPS and centriolar scaffolding share determinants is unknown
   • Composition of the condensates beyond PKP2 not defined
4. 2026 Medium

   Reinforced CCDC120 as the centrosomal targeting mediator for CEP170 by showing CEP170 C-terminal truncations lose centrosomal/microtubule localization through disrupted CCDC120 binding.

   Evidence Co-IP, localization with CEP170 truncation constructs, and microtubule regrowth assays in CRISPR CEP170-KO cells

   PMID:41888776

   Open questions at the time

   • CCDC120 interaction is a secondary finding within a CEP170-focused study
   • Binding interface on CCDC120 not mapped
   • Functional consequence for CCDC120 itself not directly tested

• How a single coiled-coil scaffold is partitioned among centrioles, neuronal vesicles, and cardiac desmosomes, and what regulates this compartment switching, remains unresolved.
• No structural model of CCDC120
• No mechanism linking its distinct localizations
• Tissue-specific expression and isoform usage not characterized