TY - JOUR
T1 - Asymmetric distribution and spatial switching of dynein activity generates ciliary motility
AU - Lin, Jianfeng
AU - Nicastro, Daniela
N1 - Funding Information:
We thank D. T. N. Chen and Z. Dogic (Brandeis University) for providing sea urchin sperm, suggestions on ATP reactivation of axonemes, and a light microscopy movie of a swimming sperm cell (Movie 1). We are grateful to C. Xu for providing electron microscopy training and management of the electron microscopy facility at Brandeis University, M. Porter (University of Minnesota) for providing the anti-IC138 antibody, K. Jaqaman (University of Texas Southwestern Medical Center) for experimental suggestions, and the team from XVIVO Scientific Animations for Movie 1. We are also grateful to W. J. Snell, M. Henne, S. Schmid (University of Texas Southwestern Medical Center), M. Porter, and C. Barber for critically reading the manuscript. We also acknowledge P. Satir, I. Gibbons, C. Brokaw, and others in the cilia field for their pioneering studies of ciliary motility. Funding: This work was supported by funding from the National Institutes of Health (GM083122 to D.N.) and March of Dimes Foundation (to D.N.).
Publisher Copyright:
© The Authors.
PY - 2018/4/27
Y1 - 2018/4/27
N2 - Motile cilia and flagella are essential, highly conserved organelles, and their motility is driven by the coordinated activities of multiple dynein isoforms. The prevailing “switch-point” hypothesis posits that dyneins are asymmetrically activated to drive flagellar bending. To test this model, we applied cryo–electron tomography to visualize activity states of individual dyneins relative to their locations along beating flagella of sea urchin sperm cells. As predicted, bending was generated by the asymmetric distribution of dynein activity on opposite sides of the flagellum. However, contrary to predictions, most dyneins were in their active state, and the smaller population of conformationally inactive dyneins switched flagellar sides relative to the bending direction. Thus, our data suggest a “switch-inhibition” mechanism in which force imbalance is generated by inhibiting, rather than activating, dyneins on alternating sides of the flagellum.
AB - Motile cilia and flagella are essential, highly conserved organelles, and their motility is driven by the coordinated activities of multiple dynein isoforms. The prevailing “switch-point” hypothesis posits that dyneins are asymmetrically activated to drive flagellar bending. To test this model, we applied cryo–electron tomography to visualize activity states of individual dyneins relative to their locations along beating flagella of sea urchin sperm cells. As predicted, bending was generated by the asymmetric distribution of dynein activity on opposite sides of the flagellum. However, contrary to predictions, most dyneins were in their active state, and the smaller population of conformationally inactive dyneins switched flagellar sides relative to the bending direction. Thus, our data suggest a “switch-inhibition” mechanism in which force imbalance is generated by inhibiting, rather than activating, dyneins on alternating sides of the flagellum.
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U2 - 10.1126/science.aar1968
DO - 10.1126/science.aar1968
M3 - Article
C2 - 29700238
AN - SCOPUS:85046041426
VL - 360
JO - Science
JF - Science
SN - 0036-8075
IS - 6387
M1 - eaar1968
ER -