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BBS4

Tuesday 11 May 2004

Function

- BBS4, as BBS8, localizes to the centriolar satellites of centrosomes and basal bodies of primary cilia, where it functions as an adaptor of the p150(glued) subunit of the dynein transport machinery to recruit PCM1 (pericentriolar material 1 protein) and its associated cargo to the satellites.

- In vitro and in vivo studies have demonstrated that BBS4 is required for the correct localization of PCM1 to the pericentriolar satellites and that depletion of BBS4 through RNAi leads to microtubule network disorganization.

Pathology

- germline mutations in Bardet-Biedl syndrome BBS4 type.

Pathogenesis

- The loss of BBS4 function impedes ciliary function, which manifests as established ciliary phenotypes (for example, retinal dystrophy, situs inversus and cystic kidneys).

- The loss of BBS4 function also perturbs dendritic transport. This might explain some of the neuronal phenotypes seen not only in BBS, but also in other established centrosomal disorders, such as Alstrom syndrome, or suspected centrosomal or basal body disorders (by virtue of phenotypic overlap) such as Cohen syndrome and Meckel-Gruber syndrome.

- Silencing of BBS4 induces PCM1 mislocalization and concomitant deanchoring of centrosomal microtubules, arrest in cell division and apoptotic cell death. Defective targeting or anchoring of pericentriolar proteins and microtubule disorganization contribute to the BBS phenotype (15107855)