Stowe, T.R., Wilkinson, C.J., Iqbal, A., and Stearns, T. (2012) The centriolar satellite proteins Cep72 and Cep290 interact and are required for recruitment of BBS proteins to the cilium. Molecular biology of the cell. 23(17):3322-3335.
Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Centriolar
satellites are centrosome-associated structures, defined by the protein PCM1, that are implicated in centrosomal protein trafficking.
We identify Cep72 as a PCM1-interacting protein required for recruitment of the ciliopathy-associated protein, Cep290, to
centriolar satellites. Loss of centriolar satellites by depletion of PCM1 causes relocalization of Cep72 and Cep290 from satellites
to the centrosome, suggesting that their association with centriolar satellites normally restricts their centrosomal localization.
We identify interactions between PCM1, Cep72 and Cep290 and find that disruption of centriolar satellites by overexpression
of Cep72 results in specific aggregation of these proteins and the BBSome component, BBS4. During ciliogenesis, BBS4 relocalizes
from centriolar satellites to the primary cilium. This relocalization occurs normally in the absence of centriolar satellites
(PCM1 depletion), but is impaired by depletion of Cep290 or Cep72, resulting in defective ciliary recruitment of the BBSome
subunit BBS8. We propose that Cep290 and Cep72 in centriolar satellites regulate the ciliary localization of BBS4, which in
turn affects assembly and recruitment of the BBSome. Finally, we show that loss of centriolar satellites in zebrafish leads
to phenotypes consistent with cilium dysfunction and analogous to human ciliopathies.