Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins

As the field of cilia biology has exploded over the past decade, our understanding has evolved from the initial realization of cilia as important cellular structures to the knowledge that defects in these organelles constitute a unifying framework in numerous syndromic diseases, collectively called ciliopathies. More recently, distinct sets of genes have been identified as causing overlapping symptom clusters, making it possible to link specific genetic mutations to clinical diagnosis. Amidst this rapid progress, confusion arose because disease conditions manifest as a continuum of disorders with varying severity and organ involvement rather than cleanly segregated entities. As a result, even identical gene mutations can give rise to distinct clinical manifestations, while a well-defined clinical syndrome can trace its etiologic origin to a multitude of gene defects. The goal of this review is to focus on the differences among ciliopathies based on molecular and genetic characteristics and on the realization that assigning a specific clinical diagnosis is only the starting point for identifying the culprit gene. In reaching a clear understanding of molecular mechanisms and future therapeutic strategies, correlating specific symptoms to genetic mutation(s) should provide valuable insights.We have focused on ciliopathies that include retinal degeneration as part of the clinical spectrum in order to provide a comprehensive analysis of their mutations, phenotypes, subcellular localization of the gene products, and functional insights from respective mouse models. In addition to summarizing the current state of knowledge, we have attempted to define gaps in our understanding of cilia biology and suggested approaches for future investigations.Cilia can be categorized as primary, sensory or motile. Nearly all cells develop a primary cilium, which serves either as a precursor to a cluster of motile cilia (in cells such as ventricular ependyma and tracheal epithelium) [1,2]