Transport of Ciliary Membrane Proteins

Abstract

Cilia and flagella are highly conserved organelles in eukaryotic cells that drive cell movement and act as cell antennae that receive and transmit signals. In addition to receiving and transducing external signals that activate signal cascades, cilia also secrete ciliary ectosomes that send signals to recipient cells, and thereby mediate cell-cell communication. Abnormal ciliary function leads to various ciliopathies, and the precise transport and localization of ciliary membrane proteins are essential for cilium function. This review summarizes current knowledge about the transport processes of ciliary membrane proteins after their synthesis at the endoplasmic reticulum: modification and sorting in the Golgi apparatus, transport through vesicles to the ciliary base, entrance into cilia through the diffusion barrier, and turnover by ectosome secretion. The molecular mechanisms and regulation involved in each step are also discussed. Transport of ciliary membrane proteins is a complex, precise cellular process coordinated among multiple organelles. By systematically analyzing the existing research, we identify topics that should be further investigated to promote progress in this field of research.

Keywords: cilia; ciliary ectosome; ciliary membrane protein; ciliopathies; diffusion barrier.

FIGURE 1

Model of ciliary membrane protein transport. (1) Targeting to cilia by ciliary targeting sequences (CTSs). (2) Targeting to cilia by the late endosomal (LE) pathway. (3) Targeting to cilia or PM by lipid acylation and special carriers. (4) Targeting to cilia by specific lipid raft vesicles (unproven). (5) Targeting to cilia or PM by COPII-mediated exit from the ER. (6) Transport to the PM followed by lateral transport into cilia when cell signaling is activated. (7) Recycling pathway of ciliary membrane proteins that first reach the PM: endocytosis followed by polarized exocytosis at the periciliary membrane. (8) Transport through the diffusion barrier (DB) and entrance into cilia through the IFT-A/TULP3 complex. (9) Transport out of cilia by the IFT-B/BBSome complex. (10) The secretion of ciliary ectosomes regulates ciliary membrane protein homeostasis.