RPGRIP1L helps to establish the ciliary gate for entry of proteins.

Mutations in transition zone genes change the composition of the ciliary proteome. We isolated new mutations in (denotated as in algae) that affect the localization of the transition zone protein NPHP4 in the model organism NPHP4 localization is not affected in multiple new intraflagellar transport (IFT) mutants. We compared the proteome of cilia from wild-type and mutants that affect the transition zone () or IFT ( and ) by mass spectrometry. The mutant cilia show the most dramatic increase in cytoplasmic proteins. These nonciliary proteins function in translation, membrane remodeling, ATP production and as chaperonins. These proteins are excluded in isolated cilia from (IFT172) and (DHC1b). Our data support the idea that RPGRIP1L, but not IFT proteins, acts as part of the gate for cytoplasmic proteins. The cilia lack only a few proteins, which suggests that RPGRIP1L only has a minor role of in the retention of ciliary proteins. The mutant shows the greatest loss/reduction of proteins, and one-third of these proteins have a transmembrane domain. Hence, IFT172 may play a role in the retention of proteins.