Characterization of ubiquitin dynamics in mice photoreceptors

Primary cilia are hair-like protrusions of the plasma membrane that function as signaling hubs. The outer segment of light-sensing cells (photoreceptors) in vertebrate eyes is a modified form of primary cilium. Bardet-Biedl Syndrome (BBS) is a Mendelian disorder caused by defective protein trafficking in and out of the primary cilium. BBS proteins are either part of or activity regulators of a protein complex called the BBSome. In the absence of the BBSome, proteins accumulate inside the outer segment, leading to photoreceptor death and subsequent vision loss. While the effects of BBSome loss in photoreceptors are well-characterized, the detailed mechanism of how BBSome functions in the outer segment remains poorly understood. I have characterized the role of a small protein, ubiquitin, inside BBSome-deficient outer segments. Ubiquitin is well known for its function in tagging proteins for destruction or for regulatory fates, depending on the type of polyubiquitin chain assembled. In this study, I observed that specific types of polyubiquitin chains accumulate within the outer segment in the absence of functional BBSome. This result suggested that the ubiquitinated proteins fail to be transported back to the cell body. I further identified the ubiquitin-marked proteins and demonstrated that BBSome recognizes specific polyubiquitin chains inside the outer segments in wild-type photoreceptors. This modality of BBSome function regulates the continuous clearance of tagged proteins and therefore maintains the integrity of the photoreceptors.