The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella.
Cilia and flagella are highly conserved microtubule (MT)-based organelles with motile and sensory functions, and ciliary defects have been linked to several human diseases. The 9 + 2 structure of motile axonemes contains nine MT doublets interconnected by nexin links, which surround a central pair of singlet MTs. Motility is generated by the orchestrated activity of thousands of dynein motors, which drive interdoublet sliding. A key regulator of motor activity is the dynein regulatory complex (DRC), but detailed structural information is lacking. Using cryoelectron tomography of wild-type and mutant axonemes from Chlamydomonas reinhardtii, we visualized the DRC in situ at molecular resolution. We present the three-dimensional structure of the DRC, including a model for its subunit organization and intermolecular connections that establish the DRC as a major regulatory node. We further demonstrate that the DRC is the nexin link, which is thought to be critical for the generation of axonemal bending.
Heuser
Thomas
T
Biology Department, Brandeis University, Waltham, MA 02453, USA.
Raytchev
Milen
M
Krell
Jeremy
J
Porter
Mary E
ME
Nicastro
Daniela
D
D056444:Axonemal Dyneins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D001665:Binding Sites; D002465:Cell Movement / Q000235:genetics; D016825:Chlamydomonas reinhardtii / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D002923:Cilia / Q000737:chemistry / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D005407:Flagella / Q000737:chemistry / Q000648:ultrastructure*; D005838:Genotype; D021621:Imaging, Three-Dimensional; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000235:genetics
D008869:Microtubule-Associated Proteins; C484652:microtubule nexin; D056444:Axonemal Dyneins