| 2015 |
ODA8 (LRRC56 ortholog in Chlamydomonas) is required for cytoplasmic preassembly of outer dynein arm (ODA) complexes; dynein in oda8 mutant cytoplasm has not properly preassembled and cannot bind normally onto axonemes. ODA8 distribution between cytoplasm and flagella mirrors IFT proteins, and ~half of flagellar ODA8 is in the soluble matrix fraction, supporting a role in dynein assembly/transport rather than axonemal docking. Dynein extracted from wild-type axonemes rebinds to oda8 mutant axonemes without re-binding of ODA8, further excluding a docking role. |
Positional cloning, flagellar fractionation, in vitro dynein rebinding assays, cytoplasmic ODA preassembly assays, phylogenomics |
Cytoskeleton (Hoboken, N.J.) |
High |
25558044
|
| 2018 |
LRRC56 physically interacts with the IFT protein IFT88 (demonstrated by co-immunoprecipitation). In Trypanosoma brucei, LRRC56 is recruited to the cilium during axoneme construction, co-localizes with IFT trains, and is required for the addition of outer dynein arms to the distal end of the flagellum. Loss-of-function (null) or the p.Leu259Pro variant (equivalent to human p.Leu140Pro) causes abnormal ciliary beat patterns and absence of outer dynein arms restricted to the distal portion of the axoneme. |
Co-immunoprecipitation (LRRC56–IFT88), LRRC56-null and point-mutant T. brucei models, immunofluorescence co-localization with IFT trains, transmission electron microscopy, high-speed video microscopy |
American journal of human genetics |
High |
30388400
|
| 2024 |
In Trypanosoma brucei, LRRC56 is a transient IFT cargo during flagellum construction and is required for efficient attachment of a subset of docking complex proteins (specifically those present in the distal portion of the organelle). The relationship is interdependent: knockdown of the distal docking complex also prevents LRRC56 association with the flagellum. lrrc56−/− cells display shorter flagella with delayed maturation. Inhibition of cell division compensates for distal ODA absence by redistributing the proximal docking complex, restoring ODA attachment but not flagellum length. |
LRRC56 knockout in T. brucei, IFT co-localization assays, docking complex knockdown epistasis, transmission electron microscopy, immunofluorescence, cell-division inhibition rescue experiment |
Molecular biology of the cell |
High |
38865178
|
| 2013 |
In Chlamydomonas, ODA8 (LRRC56 ortholog) flagellar localization depends on ODA5 and ODA10; ODA10 is present on oda8-mutant flagella at wild-type levels, establishing that ODA8 acts downstream of ODA5/ODA10 for dynein arm assembly. Genetic interaction among ODA5, ODA8, and ODA10 loci was confirmed. |
Positional cloning of ODA10, immunofluorescence of ODA10p on oda8-mutant flagella, genetic interaction/epistasis analysis |
Molecular biology of the cell |
Medium |
24088566
|
| 2025 |
In Xenopus laevis multiciliated cells, loss of lrrc56 causes specific depletion of outer dynein arms (ODAs) from the distal axoneme. In vivo affinity purification–mass spectrometry revealed that Lrrc56 physically interacts with ODA docking complex components including Odad3. Lrrc56 knockdown also leads to distal loss of Odad3. Disease-associated variants in LRRC56 and ODAD3 disrupt their localization and interaction, placing both proteins in a shared functional pathway for distal ODA and docking complex deployment. |
Targeted knockdown in Xenopus laevis multiciliated cells, in vivo affinity purification–mass spectrometry (AP-MS), in vivo imaging, disease-variant functional analysis |
Disease models & mechanisms |
High |
41229303
|
| 2025 |
LRRC56 preprint (bioRxiv version): same findings as the peer-reviewed paper — Lrrc56 binds Odad3 (ODA docking complex component) by in vivo AP-MS; lrrc56 knockdown in Xenopus depletes ODAs and Odad3 specifically from the distal axoneme; disease-associated variants in LRRC56 and ODAD3 disrupt their localization and interaction. |
In vivo AP-MS, targeted knockdown, in vivo imaging in Xenopus laevis |
bioRxivpreprint |
Medium |
40631331
|
| 2025 |
LRRC56-knockout mice (CRISPR/Cas9 targeting exons 4–5) show absence of both inner dynein arm marker DNALI1 and outer dynein arm marker DNAI2 in cilia by immunofluorescence, and transmission electron microscopy reveals dynein arm defects and disorganized axonemal structure in flagella, establishing LRRC56 as required for dynein arm assembly in vivo in a mammalian model. |
CRISPR/Cas9 knockout mouse, transmission electron microscopy, immunofluorescence with dynein arm markers (DNALI1, DNAI2) |
Biology open |
High |
39912490
|
| 2025 |
Quantitative proteomic analysis of Lrrc56-knockout mouse tissues revealed markedly reduced expression of microtubule inner proteins (MIPs) and axonemal dynein assembly factors compared to wild-type, indicating LRRC56 is required for the normal abundance of multiple cilia-associated structural proteins beyond dynein arms alone. |
CRISPR/Cas9 Lrrc56-knockout mice, quantitative proteomics of ciliary tissues |
Frontiers in genetics |
Medium |
41477643
|
| 2025 |
LRRC56 interacts with IFT88 in breast cancer cells and regulates YAP1 expression via modulation of the RhoA/ROCK signaling pathway; LRRC56 overexpression promotes proliferation, migration, invasion, and EMT, while downregulation inhibits xenograft tumor growth and lung metastasis. |
In vitro functional assays (proliferation, migration, invasion), in vivo xenograft mouse model, co-immunoprecipitation (LRRC56–IFT88), western blotting for RhoA/ROCK/YAP1 pathway components, EMT markers |
Molecular biomedicine |
Medium |
40388100
|
| 2024 |
In Chlamydomonas, double heterozygosity for oda8 (LRRC56 ortholog) and pf23 (DNAAF4 ortholog) reduces cilia assembly in a sensitized (protein-synthesis-inhibited) assay, demonstrating dosage-dependent genetic interaction between LRRC56 and DNAAF4 in outer and inner dynein arm assembly. |
Second-site non-complementation screen in Chlamydomonas diploids, ciliary assembly assay under cycloheximide, immunoblotting for PF23 levels |
PLoS genetics |
Medium |
38498551
|