Trafficking in and to the primary cilium

Abstract

Polarized vesicle trafficking is mediated by small GTPase proteins, such as Rabs and Arls/Arfs. These proteins have essential roles in maintaining normal cellular function, in part, through regulating intracellular trafficking. Moreover, these families of proteins have recently been implicated in the formation and function of the primary cilium. The primary cilium, which is found on almost every cell type in vertebrates, is an organelle that protrudes from the surface of the cell and functions as a signaling center. Interestingly, it has recently been linked to a variety of human diseases, collectively referred to as ciliopathies. The primary cilium has an exceptionally high density of receptors on its membrane that are important for sensing and transducing extracellular stimuli. Moreover, the primary cilium serves as a separate cellular compartment from the cytosol, providing for unique spatial and temporal regulation of signaling molecules to initiate downstream events. Thus, functional primary cilia are essential for normal signal transduction. Rabs and Arls/Arfs play critical roles in early cilia formation but are also needed for maintenance of ciliary function through their coordination with intraflagellar transport (IFT), a specialized trafficking system in primary cilia. IFT in cilia is pivotal for the proper movement of proteins into and out of this highly regulated organelle. In this review article, we explore the involvement of polarized vesicular trafficking in cilia formation and function, and discuss how defects in these processes could subsequently lead to the abnormalities observed in ciliopathies.

Overlap of abnormal photoreceptor development and progressive degeneration in Leber congenital amaurosis caused byNPHP5mutation

“…On the other hand, as rods have a full complement of OS before the retina fully degenerates, yet loses rod function much earlier it is, an indication that there is a dissociation of structure and function. This likely results from impaired trafficking of key phototransduction proteins through the photoreceptor sensory cilium, and is reflected by the extensive rod opsin, as well as S-cone opsin, mislocalization into the inner segment and ONL (36,37). This abnormality may not be restricted solely to trafficking between IS to OS, as in the bbs4 null mouse there is impaired synaptic transmission as well which contributes to abnormalities in ERG rod b-wave (37).…”

Regulation of polycystin-1 ciliary trafficking by motifs at its C-terminus and polycystin-2 but not cleavage at GPS site

“…They are required for the photoreceptor rhodopsin to traffic to the primary cilia, and have been proposed to represent a general mechanism for ciliary targeting of membrane proteins (Hsiao et al, 2012). PC1 has been reported to bind to Arf4 and Asap1, an Arf GTPase-activating protein, and short hairpin RNA (shRNA)-mediated depletion of either protein affects the ciliary trafficking of the CD16.7-PC1 chimeric construct (Ward et al, 2011).…”

Cilia and coordination of signaling networks during heart development

“…21,136,142 A variety of different vesicle trafficking pathways regulate the assembly, maintenance, and sensory function of cilia. 143,144 Often, the proximal part of the cilium is placed within an invagination of the plasma membrane known as the ciliary pocket, which functions as the ciliary platform for exocytosis of Golgi-derived vesicles and for clathrin-dependent endocytosis (CDE). 145 Available evidence suggests that exocytosis is required for the targeting of transmembrane receptors and ion channels to the ciliary membrane, and CDE may regulate ciliary signaling through the internalization and/or recycling of receptors at the ciliary base.…”