Gated entry into the ciliary compartment

Abstract

Cilia and flagella play important roles in cell motility and cell signaling. These functions require that the cilium establishes and maintains a unique lipid and protein composition. Recent work indicates that a specialized region at the base of the cilium, the transition zone, serves as both a barrier to entry and a gate for passage of select components. For at least some cytosolic proteins, the barrier and gate functions are provided by a ciliary pore complex (CPC) that shares molecular and mechanistic properties with nuclear gating. Specifically, nucleoporins of the CPC limit the diffusional entry of cytosolic proteins in a size-dependent manner and enable the active transport of large molecules and complexes via targeting signals, importins, and the small G protein Ran. For membrane proteins, the septin protein SEPT2 is part of the barrier to entry whereas the gating function is carried out and/or regulated by proteins associated with ciliary diseases (ciliopathies) such as nephronophthisis (NPHP), Meckel-Gruber Syndrome (MKS) and Joubert Syndrome (JBTS). Here, we discuss the evidence behind these models of ciliary gating as well as the similarities to and differences from nuclear gating.

Protein Interaction Analysis Provides a Map of the Spatial and Temporal Organization of the Ciliary Gating Zone

“…The fact that Nup93 is unable to interact with the axoneme-associated motor KIF17 or the transmembrane protein SSTR3 (Figure 2F) suggests that Nup93 occupies a central position in the inner-outer axis of the ciliary gating zone (Figure 2G). These results also provide strong support for the model that NUP components play a functional role in ciliary gating [3,4]. …”

Endocytic Control of Cellular Signaling at the Primary Cilium

“…The ciliary membrane is continuous with the cell body plasma membrane, but the transition zone at the ciliary base functions as a diffusion barrier and selective gate for the passage of soluble and membrane-bound components into and out of the ciliary compartment, thereby endowing cilia with a unique protein and lipid composition ( Figure 1A) [15][16][17][18]. In many cell types and organisms, such as Trypanosoma and mammalian fibroblasts, the proximal region of the cilium is surrounded by a cytoplasmic invagination of the periciliary membrane, known as the ciliary pocket (CiPo; Figures 1A and 2), which serves as a hotspot for exo-and endocytosis of vesicles for the delivery and retrieval of ciliary membrane components [19].…”

Calmodulin regulates a TRP channel (ADF1) and phospholipase C (PLC) to mediate elevation of cytosolic calcium during acidic stress that induces deflagellation inChlamydomonas

“…How CaM participates in flagellar assembly remains a question to be answered. CaM may be involved in delivery of flagellar precursors at the flagellar base because CaM is involved in the nuclear import of proteins, and a nuclear pore-like structure has been hypothesized to be present at the flagellar base (63,64). CaM may also regulate IFT cargo delivery through an interaction with kinesin motors (65).…”