An Overview of the Primary Cilium and RPGRIP1L: The Signalling Hub’s Anchor for Organ Development and Homeostasis




cilia syndromes, ciliogenesis, ciliopathies, primary cilia, RPGRIP1L, transition zone


Research on the primary cilium has been growing exponentially in the past several decades due to its functions as a cell signalling hub, which defects leads to several disorders and abnormalities collectively known as ciliopathies. Among other parts of the primary cilium structures, the transition zone is the area whose defects lead to the most severe clinical manifestations and high lethality. The ciliary transition zone consists of multiple protein modules that are hypothesized to be anchored by the RPGRIP1L protein. Despite its importance, RPGRIP1L studies remain hidden from the limelight, and our understanding of the protein remains scattered. This review summarizes the clinical manifestations and molecular mechanisms of the RPGRIP1L in the primary cilium. We then take a closer look at each RPGRIP1L’s protein domain to understand how each domain ensures proper functions and localization of RPGRIP1L. The three domains of RPGRIP1L are postulated to be involved in different roles. While the coiled coil domain is vital for scaffolding the protein to the centriolar structure, the ability of the C2 domain to interact with lipid allows the formation of ‘lipid gate’ at the transition zone. The high variability of the RPGR interaction domain enable the RPGRIP1L to interact with multiple different proteins, making it an ideal anchor for other ciliary protein modules in the transition zone.


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