Intraflagellar Transport Proteins as Regulators of Primary Cilia Length.

Wei Wang,Brittany M Jack,Pamela V Tran,Robin L Maser,Henry H Wang,Matthew A Kavanaugh

doi:10.3389/fcell.2021.661350

Wei Wang, Brittany M Jack + Show 4 more

Open Access

https://doi.org/10.3389/fcell.2021.661350

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Abstract

Primary cilia are small, antenna-like organelles that detect and transduce chemical and mechanical cues in the extracellular environment, regulating cell behavior and, in turn, tissue development and homeostasis. Primary cilia are assembled via intraflagellar transport (IFT), which traffics protein cargo bidirectionally along a microtubular axoneme. Ranging from 1 to 10 μm long, these organelles typically reach a characteristic length dependent on cell type, likely for optimum fulfillment of their specific roles. The importance of an optimal cilia length is underscored by the findings that perturbation of cilia length can be observed in a number of cilia-related diseases. Thus, elucidating mechanisms of cilia length regulation is important for understanding the pathobiology of ciliary diseases. Since cilia assembly/disassembly regulate cilia length, we review the roles of IFT in processes that affect cilia assembly/disassembly, including ciliary transport of structural and membrane proteins, ectocytosis, and tubulin posttranslational modification. Additionally, since the environment of a cell influences cilia length, we also review the various stimuli encountered by renal epithelia in healthy and diseased states that alter cilia length and IFT.

Highlights

Cilia or flagella are evolutionarily conserved organelles that protrude from a wide range of eukaryotic cells, from single-celled protists, like Chlamydomonas reinhardtii, to almost every vertebrate cell
Since posttranslational modification of axonemal tubulin can promote cilia assembly or disassembly, we review the effects of glutamylation and O-GlcNAcylation on intraflagellar transport (IFT)
The IFT-A core binds to the tubbyrelated protein 3 (TULP3), which acts like an adaptor to import a subset of G protein-coupled receptors (GPCRs) into primary cilia

Summary

Introduction

Cilia or flagella are evolutionarily conserved organelles that protrude from a wide range of eukaryotic cells, from single-celled protists, like Chlamydomonas reinhardtii, to almost every vertebrate cell. Ciliary ARL13B is lost in Ift144 knockout and Ift43 knockdown cells and reduced in Thm1-null mouse embryonic fibroblasts (MEFs) (Liem et al, 2012; Fu et al, 2016; Wang et al, 2020).

Results

Conclusion