Lechtreck et al. describe how a protein complex linked to human disease helps export signaling proteins out of cilia.
Bardet-Biedl syndrome (BBS) is associated with mutations in several cilia proteins, seven of which form a complex called the BBSome. In model organisms from mice to the green alga Chlamydomonas, the loss of BBS proteins causes various signaling proteins to either accumulate in or disappear from cilia, suggesting that the BBSome regulates the export and/or import of ciliary proteins.
Lechtreck et al. found that, in algae lacking BBS4, the signaling enzyme phospholipase D (PLD) gradually accumulated to 150 times its level in wild-type cilia, changing the ciliary membrane’s lipid composition. Reintroducing wild-type BBS4 induced the rapid removal of excess PLD from cilia, demonstrating that the BBSome is involved in PLD export. The BBSome doesn’t work alone, however. The BBSome moves up and down cilia in association with both retrograde and anterograde intraflagellar transport (IFT) particles. Algae lacking retrograde IFT proteins also accumulated PLD in their cilia, despite the presence of intact BBSomes.
Lechtreck et al. therefore think that the BBSome acts as a cargo adaptor linking PLD and other proteins to retrograde IFT particles as they move out of cilia. BBS proteins weren’t required for PLD’s entry into cilia, but whether the BBSome imports other cilia proteins remains unclear. The enzyme carbonic anhydrase 6, for example, disappeared gradually from BBS4 mutant cilia, suggesting that its loss could be an indirect consequence of defective export rather than a direct result of impaired import.
Text by Ben Short