| 2001 |
KIFC3 is a minus end-directed microtubule motor protein that localizes to Triton X-100-insoluble (lipid raft) membrane organelles beneath the apical plasma membrane of polarized epithelial cells and co-immunoprecipitates and co-localizes with annexin XIIIb on apically transported TGN-derived vesicles. Overexpression of dominant-negative (motor-domainless) KIFC3 partially inhibited apical transport of influenza hemagglutinin and annexin XIIIb, while full-length KIFC3 overexpression accelerated it. |
Flotation assay with detergent extraction, immunoprecipitation, GST pulldown, dominant-negative overexpression in MDCK II cells, immunoelectron microscopy |
The Journal of cell biology |
High |
11581287
|
| 2002 |
KIFC3 is associated with the Golgi apparatus in adrenocortical cells and is required for Golgi positioning and integration: knockout of kifC3 causes Golgi fragmentation under cholesterol-depleted conditions due to markedly reduced inward (minus-end-directed) motility of Golgi fragments. KIFC3 acts complementarily with cytoplasmic dynein in this process, and its absence exacerbates Golgi scattering caused by dynamitin overexpression even when cholesterol is present. |
kifC3 knockout mouse (homologous recombination), live-cell microscopy of Golgi fragment motility, dynamitin overexpression epistasis |
The Journal of cell biology |
High |
12135985
|
| 2001 |
Mouse KifC3 is a ubiquitously expressed C-terminal (minus end-directed) kinesin. Homozygous knockout mice are viable, reproduce normally, and develop normally, indicating KifC3 is dispensable for normal development and reproduction. |
cDNA cloning from mouse brain library, homologous recombination knockout in embryonic stem cells, phenotypic analysis of homozygous mutants |
Molecular and cellular biology |
Medium |
11154264
|
| 2013 |
KIFC3 localizes to the central spindle bridge during cytokinesis in a motor-dependent manner and promotes efficient cytokinesis by congressing microtubules at the central bridge. Perturbation of KIFC3 function widens and extends the central bridge and delays abscission. In interphase, KIFC3 caps microtubules released from the centrosome. |
Loss-of-function perturbation, live-cell microscopy, immunofluorescence localization during cell cycle stages |
Cell cycle (Georgetown, Tex.) |
Medium |
24275865
|
| 2013 |
KifC3 interacts with the peroxisomal AAA-ATPase PEX1, confirmed by co-immunoprecipitation and co-localization in cells. RNAi knockdown of KifC3 causes perinuclear clustering of peroxisomes in a microtubule-dependent manner, suggesting KifC3 regulates minus-end-directed peroxisomal transport, potentially by antagonizing dynein-driven inward movement. |
Yeast two-hybrid (initial identification), co-immunoprecipitation, immunofluorescence co-localization, RNAi knockdown with organelle distribution readout |
Biochimica et biophysica acta |
Medium |
23954441
|
| 2014 |
KIFC3 moves into adherens junctions (AJs) via microtubules nucleated from CAMSAP3 (Nezha) clusters and recruits the deubiquitinase USP47 to AJs. Depletion of KIFC3 or USP47 leads to increased E-cadherin ubiquitination (by Hakai E3 ligase), cleavage at a juxtamembrane region producing a 90-kDa fragment, and E-cadherin internalization. KIFC3 thus suppresses E-cadherin degradation by maintaining USP47 at AJs. |
Co-immunoprecipitation (KIFC3–USP47 interaction), RNAi knockdown of KIFC3/USP47, proteasome inhibitor rescue, E-cadherin ubiquitination assay, immunofluorescence |
Molecular biology of the cell |
High |
25253721
|
| 2019 |
KIFC3 forms a homotetramer that provides microtubule-based centrosome cohesion during mitotic onset, pulling two centrosomes together via a specific microtubule network. KIFC3-mediated cohesion counteracts EG5-driven separation forces to prevent premature spindle formation after linker dissolution. KIFC3 is inactivated by NEK2 kinase to allow bipolar spindle assembly. Persistent centrosome cohesion in mitosis causes chromosome mis-segregation. |
KIFC3 knockout/depletion, biochemical characterization of homotetramer assembly, live-cell microscopy of centrosome dynamics, epistasis with EG5 and NEK2, chromosome segregation assay |
Nature cell biology |
High |
31481795
|
| 2020 |
KIFC3 has a dendrite-specific distribution in neurons and interacts with the microtubule minus-end binding protein CAMSAP2. Depletion of KIFC3 or CAMSAP2 increases microtubule dynamics during dendritic development. CAMSAP2 anchors KIFC3 at microtubule minus ends to immobilize microtubule arrays in dendrites, organizing the mixed anti-parallel microtubule polarity characteristic of dendrites. |
Co-immunoprecipitation (KIFC3–CAMSAP2 interaction), shRNA knockdown in neurons, live imaging of microtubule dynamics, immunofluorescence for KIFC3 dendritic distribution |
Current biology : CB |
High |
32084403
|
| 2024 |
KIFC3 is essential for spindle assembly and cytokinesis during mouse oocyte meiosis. KIFC3 localizes to centromeres at metaphase I and translocates to the midbody at telophase I. Disruption of KIFC3 causes defective polar body extrusion, aberrant meiotic spindles, chromosome misalignment, and loss of kinetochore-microtubule attachment associated with failed BubR1/Bub3 recruitment. KIFC3 interacts with Sirt2 to maintain acetylated tubulin levels and microtubule stability, and interacts with PRC1 to regulate midbody formation. |
Immunofluorescence localization, KIFC3 activity disruption, co-immunoprecipitation (KIFC3–Sirt2, KIFC3–PRC1), acetylated tubulin assay, polar body extrusion and spindle integrity assays |
Cell communication and signaling : CCS |
Medium |
38553728
|
| 2024 |
In stressed cells undergoing senescence, KIFC3 is recruited to plus-ends of stress-induced nucleus-to-cilium microtubule arrays (sinc-MTs, which are polyglutamylated with minus-ends near the nuclear envelope) and interacts with centrosomal protein CENEXIN1. KIFC3 mediates nuclear transport of FBF1 along sinc-MTs to PML nuclear bodies. Deficiency of KIFC3 abolishes PML-NB translocation of FBF1 and CENEXIN1, and prevents senescence initiation. |
Immunofluorescence and live imaging of sinc-MTs, KIFC3 knockout/knockdown, co-immunoprecipitation (KIFC3–CENEXIN1), FBF1/CENEXIN1 translocation assay, senescence assay |
Nature communications |
High |
39266565
|
| 2024 |
KIFC3 physically interacts with PI3K p85α subunit, as confirmed by co-immunoprecipitation of endogenous and exogenous proteins, and promotes PI3K/AKT pathway activation to drive NSCLC cell proliferation, migration, and invasion. |
Co-immunoprecipitation (endogenous and exogenous KIFC3 with PI3Kp85α), western blot of pathway components, KIFC3 overexpression/knockdown with PI3K inhibitor (LY294002) rescue, xenograft tumor model |
Scientific reports |
Medium |
39227687
|
| 2024 |
KIFC3 interacts with β-catenin phosphorylated at S47 (β-catenin p-S47), with lower binding affinity observed for S47A mutant. Knockdown of KIFC3 reduces β-catenin p-S47 at the centrosome and causes primary cilia deficiency, while β-catenin p-S47 accumulates in the Golgi. KIFC3 thus participates in transport of β-catenin p-S47 from the Golgi to the centrosome to promote primary ciliogenesis. |
Co-immunoprecipitation (KIFC3–β-catenin p-S47), binding affinity comparison with S47A mutant, KIFC3 knockdown with primary cilia and β-catenin localization readout |
Molecules and cells |
Medium |
39476973
|
| 2025 |
In G1 phase, KIFC3 drives minus-end-directed compaction of ERES (endoplasmic reticulum exit sites) near the centrosome in a CDK1-signaling-dependent tug-of-war with plus-end-directed motors. In S/G2, kinesin-1 overcomes KIFC3 to allow ERES dispersion. |
Loss-of-function approaches (RNAi/knockdown), live-cell microscopy, cell cycle staging, CDK1 inhibition |
bioRxivpreprint |
Low |
|
| 2026 |
In megakaryocytes, Kifc3 acts as a minus-end-directed motor for centrosomal delivery of cargos and controls centrosomal localization of Cep192. Kifc3 knockdown in neonatal megakaryocytes causes Cep192 upregulation and dispersion from the centrosome, inducing adult-type morphogenesis with augmented platelet release. A small molecule Kifc3 inhibitor identified in silico recapitulated this effect. |
shRNA knockdown in neonatal megakaryocytes, immunofluorescence for Cep192 localization, in silico inhibitor screening with functional validation in vitro and in vivo |
bioRxivpreprint |
Low |
41929089
|