Ciliary mechanosensation – roles of polycystins and mastigonemes

Abstract

Cilia are surface-exposed organelles that provide motility and sensory functions for cells, and it is widely believed that mechanosensation can be mediated through cilia. Polycystin-1 and -2 (PC-1 and PC-2, respectively) are transmembrane proteins that can localize to cilia; however, the molecular mechanisms by which polycystins contribute to mechanosensation are still controversial. Studies detail two prevailing models for the molecular roles of polycystins on cilia; one stresses the mechanosensation capabilities and the other unveils their ligand–receptor nature. The discovery that polycystins interact with mastigonemes, the ‘hair-like’ protrusions of flagella, is a novel finding in identifying the interactors of polycystins in cilia. While the functions of polycystins proposed by both models may coexist in cilia, it is hoped that a precise understanding of the mechanism of action of polycystins can be achieved by uncovering their distribution and interacting factors inside cilia. This will hopefully provide a satisfying answer to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD), which is caused by mutations in PC-1 and PC-2. In this Review, we discuss the characteristics of polycystins in the context of cilia and summarize the functions of mastigonemes in unicellular ciliates. Finally, we compare flagella and molecular features of PC-2 between unicellular and multicellular organisms, with the aim of providing new insights into the ciliary roles of polycystins in general.

The Small Interactor of PKD2 protein promotes the assembly and ciliary entry of the Chlamydomonas PKD2–mastigoneme complexes

“…In C. elegans , the polycystin homologs LOV-1 and PKD-2 (also known as PC1 and PC2, respectively) are expressed specifically in male-specific sensory neurons; both proteins localize to primary cilia, and are required for male mating behavior ( Barr and Sternberg, 1999 ; Walsh et al, 2022 ). PKD2 is also present in non-metazoans, which typically lack PKD1 homologs, raising questions about the composition and function of PKD2 channel complexes in those species ( Liu et al, 2023 ). In fission yeast, a PKD2-like protein, which possesses nine transmembrane helices, is located in the plasma membrane, contributing to cellular Ca 2+ homeostasis.…”

“…Cleavage occurs in the cell body, and the two PKD2 fragments enter cilia, remaining associated to each other ( Huang et al, 2007 ; Liu et al, 2020 ). Inside cilia, Chlamydomonas PKD2 attaches, directly or indirectly, to the axonemal doublet microtubules (DMTs) 4 and 8 and is required for anchoring the mastigonemes, thread-like extracellular polymers of the glycoprotein MST1, to the ciliary surface ( Liu et al, 2023 , 2020 ). The ultrastructure of MST1 was recently determined (PDB: ) and is dominated by immunoglobulin-like and Sushi domains, structural elements observed in many extracellular proteins ( Wang et al, 2023 ).…”

Impaired centrosome biogenesis in kidney stromal progenitors reduces abundance of interstitial lineages and accelerates injury-induced fibrosis

“…The centrosome is the main microtubule-organizing center in mammalian cells, essential for regulating the interphase and mitotic microtubule arrays, and is indispensable for cilium formation 6 . Cilia are also microtubule-based organelles that are templated by the centrosome, and perform important chemo-and mechanosensory functions in cells 7,8,9 . Under normal physiological conditions, there is typically one centrosome-cilium complex per cell, and this number is tightly controlled 6,[10][11][12] .…”

Cep120 is essential for kidney stromal progenitor cell growth and differentiation

“…The centrosome is the main microtubule-organizing center in mammalian cells, essential for regulating the interphase and mitotic microtubule arrays, and is indispensable for cilium formation (Breslow and Holland, 2019 ). Cilia are also microtubule-based organelles that are templated by the centrosome, and perform important chemo- and mechanosensory functions in cells (Delling et al, 2016 ; Liu et al, 2023 ; Shah et al, 2009 ). Under normal physiological conditions, there is typically one centrosome-cilium complex per cell, and this number is tightly controlled (Breslow and Holland, 2019 ; Loncarek and Bettencourt-Dias, 2018 ; Nigg and Holland, 2018 ; Nigg and Stearns, 2011 ).…”