PT - JOURNAL ARTICLE AU - Karl Lechtreck AU - Yi Liu AU - Jin Dai AU - Rama A. Alkhofash AU - Jack Butler AU - Lea Alford AU - Pinfen Yang TI - <em>Chlamydomonas</em> ARMC2/PF27 is an obligate cargo adapter for IFT of radial spokes AID - 10.1101/2021.10.31.466660 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.10.31.466660 4099 - http://biorxiv.org/content/early/2021/10/31/2021.10.31.466660.short 4100 - http://biorxiv.org/content/early/2021/10/31/2021.10.31.466660.full AB - Intraflagellar transport (IFT) carries proteins into flagella but how IFT trains interact with the large number of diverse proteins required to assemble flagella remains largely unknown. Here, we show that IFT of radial spokes in Chlamydomonas requires ARMC2/PF27, a conserved armadillo repeat protein associated with male infertility and reduced lung function. Chlamydomonas ARMC2 was highly enriched in growing flagella and tagged ARMC2 and the spoke protein RSP3 comigrated on anterograde trains. In contrast, a cargo and an adapter of inner and outer dynein arms moved independently of ARMC2, indicating that unrelated cargoes distribute stochastically onto the IFT trains. After concomitant unloading at the flagellar tip, RSP3 attached to the axoneme whereas ARMC2 diffused back to the cell body. In armc2/pf27 mutants, IFT of radial spokes was abolished and the presence of radial spokes was limited to the proximal region of flagella. We conclude that ARMC2 is a cargo adapter required for IFT of radial spokes to ensure their assembly along flagella. ARMC2 belongs to a growing class of cargo-specific adapters that enable flagellar transport of preassembled axonemal substructures by IFT.Competing Interest StatementThe authors have declared no competing interest.CHXcycloheximideFPfluorescent proteinIFTintraflagellar transportNGmNeonGreenmSmScarlet-IRSradial spoke.