Trafficking in and to the primary cilium

Primary cilia are evolutionarily conserved organelles projecting from the plasma membrane in almost every vertebrate cell. In general, primary cilia serve as sensors through which cells receive signals from light, chemical, or mechanical stimuli [1]. Moreover, the involvement of primary cilia in several signaling pathways important for development and tissue homeostasis (including the Sonic hedgehog and Wnt signaling pathways) has attracted much interest and stimulated extensive studies on this ancient cellular structure [2-6]. A functional primary cilium is required to properly activate primary cilia-mediated cellular signaling. Therefore, any defects in primary cilia could lead to cellular dysfunction. Indeed, abnormalities in primary cilia have been linked to a constellation of phenotypically and genetically overlapping human diseases, which include Bardet-Biedl syndrome, Joubert syndrome, Meckel-Gruber syndrome, nephronophthisis and Sensenbrenner syndrome; all now collectively known as ciliopathies [7-10]. The clinical manifestations of these disorders can include brain malformations, skeletal abnormalities, retinal degeneration, and cystic kidney disease.The formation and function of primary cilia are tightly regulated by polarized vesicle trafficking, not only to the primary cilium, but also in coordination with trafficking throughout the entire cell [5]. Although bioinformatic, proteomic and genetic studies have suggested that more than a thousand proteins can be localized at the primary cilium, it is still unclear why and how these proteins work together in this specialized cellular compartment [11-15]. Therefore, studying the formation and function of the primary cilium, through investigations into the function of these ciliary proteins, will help to elucidate the pathophysiological mechanisms responsible for causing the ciliopathies.Cilia are categorized into two classes: motile and non-motile. Motile cilia, such as tracheal cilia, can be numerous on a cel