The Developmental Process of the Growing Motile Ciliary Tip Region

Reynolds, Matthew J.; Phetruen, Tanaporn; Fisher, Rebecca; Chen, Ke; Pentecost, Brian T.; Gomez, George; Ounjai, Puey; Sui, Haixin

doi:10.1038/s41598-018-26111-2

Cited by 17 publications

(23 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The latter two forms are unique to cilia and flagella. Although microtubule doublets were found to become singlets at the tip end of cilia or flagella (29,41,42), the doublet-singlet transitions remain structurally uncharacterized.In this work we determined complete 3D structural maps of epithelial primary cilia using serial section electron tomography (SSET) and developed a 3D structural model of typical primary cilia as an updated structural baseline for primary cilium research. We found that key features of primary cilia architecture are distinct from expectations based on the 9+0 paradigm.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Three-dimensional architecture of epithelial primary cilia

Sun

Fisher

Bowser

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

120

View full text Add to dashboard Cite

We report a complete 3D structural model of typical epithelial primary cilia based on structural maps of full-length primary cilia obtained by serial section electron tomography. Our data demonstrate the architecture of primary cilia differs extensively from the commonly acknowledged 9+0 paradigm. The axoneme structure is relatively stable but gradually evolves from base to tip with a decreasing number of microtubule complexes (MtCs) and a reducing diameter. The axonemal MtCs are cross-linked by previously unrecognized fibrous protein networks. Such an architecture explains why primary cilia can elastically withstand liquid flow for mechanosensing. The nine axonemal MtCs in a cilium are found to differ significantly in length indicating intraflagellar transport processes in primary cilia may be more complicated than that reported for motile cilia. The 3D maps of microtubule doublet-singlet transitions generally display longitudinal gaps at the inner junction between the A-and B-tubules, which indicates the inner junction protein is a major player in doublet-singlet transitions. In addition, vesicles releasing from kidney primary cilia were observed in the structural maps, supporting that ciliary vesicles budding may serve as ectosomes for cell-cell communication.primary cilium | 3D structure | electron microscopy E pithelial primary cilia are hair-like, membrane-enveloped cellular projections that extend into the extracellular space. They are sensors detecting environmental signals for modulation of cellular physiological activities. Due to the importance of these cellular activities, defects in primary cilium assembly/disassembly (ciliogenesis) and maintenance underlie many developmental and organ disorders (1-3). Accurate information of the 3D structure of primary cilia is essential to fully understand the process and regulation of primary ciliogenesis.In mammalian organs, such as kidney, liver, and pancreas, each epithelial cell carries a single primary cilium as a mechanosensor, which bends reversibly under liquid flow (4-6). The passive elastic bending of primary cilia is believed to modulate epithelial cell proliferation and autophagy, thereby maintaining the normal architecture of mature organ tissues essential to their physiological functions, although the identity of the signaling messenger is controversial (2, 7-13). The elastic bending property relies on the structure of the ciliary microtubule-based framework (axoneme). The 3D architecture of primary cilium axoneme is fundamental to understanding the mechanosensory function of primary cilia in kidney and other cells.Electron microscopic (EM) studies of both primary cilia and motile cilia started over half century ago (14-18). The primary cilium axoneme has long been described as a "9+0" architecture, with 9 peripheral microtubule doublets of the same length forming a hollow cylindric architecture as the core framework based on some electron micrographs (1,(17)(18)(19)(20)(21)(22)(23)(24). The 9+0 model is currently the most accepted structural underst...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Three-dimensional architecture of epithelial primary cilia

Sun

Fisher

Bowser

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

120

View full text Add to dashboard Cite

show abstract

“…There is an ultrastructural heterogeneity between the distal tips of different organisms . In the flagellar tips of model organisms like Chlamydomonas reinhardtii or Tetrahymena thermophila , the incomplete B‐tubules of dMTs end and the A‐tubules extend together with the CP to the tip extremity, creating the singlet region . However, this region is completely absent in other models like Leishmania mexicana and Trypanosoma brucei .…”

mentioning

confidence: 99%

Axonemal doublet microtubules can split into two complete singlets in human sperm flagellum tips

2019

View full text Add to dashboard Cite

Motile flagella are crucial for human fertility and embryonic development. The distal tip of the flagellum is where growth and intra‐flagellar transport are coordinated. In most model organisms, but not all, the distal tip includes a ‘singlet region’, where axonemal doublet microtubules (dMT) terminate and only complete A‐tubules extend as singlet microtubules (sMT) to the tip. How a human flagellar tip is structured is unknown. Here, the flagellar tip structure of human spermatozoa was investigated by cryo‐electron tomography, revealing the formation of a complete sMT from both the A‐tubule and B‐tubule of dMTs. This different tip arrangement in human spermatozoa shows the need to investigate human flagella directly in order to understand their role in health and disease.

show abstract

“…We sorted the reported flagella tip structures into six different models ( Figure 3). thermophila with three different EM techniques (18,25,26), except that its central pair microtubules extend approximately 200 nm longer than the A-tubules in the singlet region, giving the tip a more protruding shape. The bead of the central microtubule cap was not visible in the cryo-ET reconstructions of T. thermophila flagella tips (26).…”

Section: Structural Models For Distal Tips Of Motile Flagellamentioning

confidence: 99%

“…thermophila with three different EM techniques (18,25,26), except that its central pair microtubules extend approximately 200 nm longer than the A-tubules in the singlet region, giving the tip a more protruding shape. The bead of the central microtubule cap was not visible in the cryo-ET reconstructions of T. thermophila flagella tips (26). Two other species of protist ciliates shared a similar tip ultrastructure (27,28).…”

Section: Structural Models For Distal Tips Of Motile Flagellamentioning

confidence: 99%

Composition, Structure, and Function of the Eukaryotic Flagellum Distal Tip

Croft¹,

Zabeo²,

Subramanian³

et al. 2018

Preprint

View full text Add to dashboard Cite

Cilia and flagella are long extensions commonly found on the surface of eukaryotic cells. In fact, most human cells have a flagellum, and failure to correctly form cilia leads to a spectrum of diseases gathered under the name “ciliopathies”. Since cilia are so wide spread in the body, their malfunction can affect multiple organs with symptoms such as blindness, deafness, skeletal deformations, infertility and mental retardation. The cilium distal tip is where a cilium grows and signals. Therefore, the correct structure and composition of this region should be crucial to avoid the health issues associated with the ciliopathies. Yet, out of the flagellar regions, the distal tip is probably the least intensively studied. In this review, we will summarize the current knowledge on the flagellar tip structure, the dynamicity and signalling that occurs here and the proteins localizing to this important cellular region.

show abstract

The Developmental Process of the Growing Motile Ciliary Tip Region

Cited by 17 publications

References 51 publications

Three-dimensional architecture of epithelial primary cilia

Three-dimensional architecture of epithelial primary cilia

Axonemal doublet microtubules can split into two complete singlets in human sperm flagellum tips

Composition, Structure, and Function of the Eukaryotic Flagellum Distal Tip

Contact Info

Product

Resources

About