The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella

Heuser, Thomas; Raytchev, Milen; Krell, Jeremy; Porter, Mary E.; Nicastro, Daniela

doi:10.1083/jcb.200908067

Cited by 312 publications

(503 citation statements)

References 60 publications

Supporting

Mentioning

467

Contrasting

Unclassified

Order By: Relevance

“…Confocal microscopy reveals the FLAG signal along the flagella of mouse spermatozoa in agreement with other work that shows that DRC5 is located along the axoneme (Fig. 3E) (32).…”

Section: Resultssupporting

confidence: 76%

“…This complex interconnects the A tubule with the adjacent microtubule pair's B to prevent sliding between tubules from the forces generated by axonemal dynein (35). Several mutants in the nexin complex disrupt the coordinated movement of the axoneme, leading to irregular flagella beating (7,23,32,36,37).…”

Section: Resultsmentioning

confidence: 99%

“…Drc5 is the Tcte1 ortholog in these unicellular green algae. Deletion and proteomic analyses in Chlamydomonas identified DRC5 as a component of the N-DRC (23,32,33). Nexin or "bridge" was the name for a structure observed between the outer doublets of the 9+2 arrangement from electron micrographs (32,34).…”

Section: Resultsmentioning

confidence: 99%

“…Deletion and proteomic analyses in Chlamydomonas identified DRC5 as a component of the N-DRC (23,32,33). Nexin or "bridge" was the name for a structure observed between the outer doublets of the 9+2 arrangement from electron micrographs (32,34). This complex interconnects the A tubule with the adjacent microtubule pair's B to prevent sliding between tubules from the forces generated by axonemal dynein (35).…”

Section: Resultsmentioning

confidence: 99%

“…4A) (41)(42)(43). Based on cryo-electron tomography of Chlamydomonas wild-type and mutant axonemes (23,32), DRC5 (TCTE1), -3, -6, and -7 have been mapped proximal to each other within the DRC complex (Fig. 4B).…”

Section: Resultsmentioning

confidence: 99%

See 4 more Smart Citations

TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa

Castaneda

Hua

Miyata

et al. 2017

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

View full text Add to dashboard Cite

Flagella and cilia are critical cellular organelles that provide a means for cells to sense and progress through their environment. The central component of flagella and cilia is the axoneme, which comprises the "9+2" microtubule arrangement, dynein arms, radial spokes, and the nexin-dynein regulatory complex (N-DRC). Failure to properly assemble components of the axoneme leads to defective flagella and in humans leads to a collection of diseases referred to as ciliopathies. Ciliopathies can manifest as severe syndromic diseases that affect lung and kidney function, central nervous system development, bone formation, visceral organ organization, and reproduction. T-Complex-Associated-Testis-Expressed 1 (TCTE1) is an evolutionarily conserved axonemal protein present from Chlamydomonas (DRC5) to mammals that localizes to the N-DRC. Here, we show that mouse TCTE1 is testis-enriched in its expression, with its mRNA appearing in early round spermatids and protein localized to the flagellum. TCTE1 is 498 aa in length with a leucine rich repeat domain at the C terminus and is present in eukaryotes containing a flagellum. Knockout of Tcte1 results in male sterility because Tcte1-null spermatozoa show aberrant motility. Although the axoneme is structurally normal in Tcte1 mutant spermatozoa, Tcte1-null sperm demonstrate a significant decrease of ATP, which is used by dynein motors to generate the bending force of the flagellum. These data provide a link to defining the molecular intricacies required for axoneme function, sperm motility, and male fertility. male infertility | asthenozoospermia | glycolysis | mutant mouse | testis-specific gene F lagella are ancient, analogous cellular structures used for locomotion and as sensory organelles present in all three domains of life (bacteria, archaea, and eukaryotes). The advantages conferred by this organelle are highlighted by the flagella's apparent independent evolution in all three domains (1-3). Of all of the different flagella present among eukaryotes, flagella attached to gametes play a critical function in uniting gametes for fertilization and the perpetuation of a species. Mammalian spermatozoa have a specialized flagellum that contains a midpiece, principal piece, and end piece with the axoneme running along the entire length (4). The flagellum equips sperm with the capability to deliver half of the male's genetic material to the female gamete, the oocyte. In addition to flagella, eukaryotes contain another related structure called cilia. The defining feature of flagella and cilia is the axoneme, the "9+2" microtubule arraignment of two central pairs of microtubules surrounded by nine pairs of microtubule doublets (5). The microtubule motor dynein is anchored to the outer microtubules and responsible for generating the force required to produce the beating pattern of flagella and cilia (6). The force generated by dynein causes sliding of the microtubules among each other; however, the nexin complex anchors the microtubules in place. The nexin complex [or nexin-dynei...

show abstract

“…Confocal microscopy reveals the FLAG signal along the flagella of mouse spermatozoa in agreement with other work that shows that DRC5 is located along the axoneme (Fig. 3E) (32).…”

Section: Resultssupporting

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa

Castaneda

Hua

Miyata

et al. 2017

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

View full text Add to dashboard Cite

show abstract

Advances in the Diagnosis and Treatment of Primary Ciliary Dyskinesia

Dunsky

Menezes

Ferkol

2021

JAMA Otolaryngol Head Neck Surg

View full text Add to dashboard Cite

IMPORTANCE Primary ciliary dyskinesia (PCD) is a rare, inherited condition involving motile cilia that line the upper and lower respiratory tracts, leading to chronic infections of the paranasal sinuses, middle ear, and bronchi that begin during infancy. Unfortunately, despite its early presentation, PCD is often recognized late.OBSERVATIONS People with PCD have diverse clinical manifestations, including chronic upper and lower respiratory tract disease, laterality defects, and subfertility. Through efforts of multinational clinical collaboratives, 4 cardinal features have been described that identify people who likely have PCD: unexplained neonatal respiratory distress, left-right laterality defects, daily wet cough, and nonseasonal rhinosinusitis beginning before 6 months of age. Recent advances in the understanding of the genetics and pathogenesis of the disease have led to a revolution in the approach to screening and diagnostic testing. Moreover, PCD has a broad clinical spectrum, and genotype-phenotype associations are beginning to be recognized. CONCLUSIONS AND RELEVANCEA high index of suspicion remains critical in diagnosing PCD.Children who have at least 2 of the major clinical features should be considered for further evaluation. Nevertheless, while newer tools have improved diagnostic capabilities, there is no single test that will diagnose every person with the disease. In people suspected of having PCD, nasal nitric oxide measurement is a useful screen, followed by diagnostic genetic testing and if negative, ciliary ultrastructural analysis. Despite otolaryngologic manifestations being common in infancy and persisting into adulthood, they have been understudied. Indeed, there are few randomized clinical trials examining the medicosurgical approaches to respiratory disease.

show abstract

Isolation of Chlamydomonas Flagella

2013

View full text Add to dashboard Cite

A simple, scalable, and fast procedure for the isolation of Chlamydomonas flagella is described. Chlamydomonas can be synchronously deflagellated by treatment with chemicals, pH shock, or mechanical shear. The Basic Protocol describes the procedure for flagellar isolation using dibucaine to induce flagellar abscission; we also describe the pH shock method as an Alternate Protocol when flagellar regeneration is desirable. Sub‐fractionation of the isolated flagella into axonemes and the membrane + matrix fraction is described in a Support Protocol. Curr. Protoc. Cell Biol. 59:3.41.1‐3.41.9. © 2013 by John Wiley & Sons, Inc.

show abstract

The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella

Abstract: Elegant cryoelectron tomography reveals that the nexin link between microtubule doublets in 9 + 2 axonemal structures, critical for their ability to bend, is the dynein regulatory complex.

Cited by 312 publications

References 60 publications

TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa

TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa

Advances in the Diagnosis and Treatment of Primary Ciliary Dyskinesia

Isolation of Chlamydomonas Flagella

Contact Info

Product

Resources

About