TY - JOUR
T1 - Proteins that control the geometry of microtubules at the ends of cilia
AU - Louka, Panagiota
AU - Vasudevan, Krishna Kumar
AU - Guha, Mayukh
AU - Joachimiak, Ewa
AU - Wloga, Dorota
AU - Tomasi, Raphaël F.X.
AU - Baroud, Charles N.
AU - Dupuis‑Williams, Pascale
AU - Galati, Domenico F.
AU - Pearson, Chad G.
AU - Rice, Luke M
AU - Moresco, James J.
AU - Yates, John R.
AU - Jiang, Yu Yang
AU - Lechtreck, Karl
AU - Dentler, William
AU - Gaertig, Jacek
N1 - Funding Information:
The research reported in this publication was supported by the National Institutes of Health, including grants R01GM089912 and R21HD092809 (to J. Gaertig), R01GM110413 (to K. Lechtreck), P41GM103533 (to J.J. Moresco and J.R. Yates III), R01GM099820 (to C.G. Pearson), and R01GM098543 (to L.M. Rice). P. Louka was supported by a predoctoral fellowship from the American Heart Association (no. 16PRE27480028). J. Gaertig was also supported by intramural grants from the Office of Vice-President for Research and the Department of Cellular Biology at the University of Georgia. R.F.-X. Tomasi and C.N. Baroud were funded by the European Research Council grant 278248 Multicell. D. Wloga was funded by the Polish National Science Centre 2014/14/M/ NZ3/00511 (Harmonia 6) grant. The authors declare no competing financial interests.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Cilia, essential motile and sensory organelles, have several compartments: the basal body, transition zone, and the middle and distal axoneme segments. The distal segment accommodates key functions, including cilium assembly and sensory activities. While the middle segment contains doublet microtubules (incomplete B-tubules fused to complete A-tubules), the distal segment contains only A-tubule extensions, and its existence requires coordination of microtubule length at the nanometer scale. We show that three conserved proteins, two of which are mutated in the ciliopathy Joubert syndrome, determine the geometry of the distal segment, by controlling the positions of specific microtubule ends. FAP256/CEP104 promotes A-tubule elongation. CHE-12/Crescerin and ARMC9 act as positive and negative regulators of B-tubule length, respectively. We show that defects in the distal segment dimensions are associated with motile and sensory deficiencies of cilia. Our observations suggest that abnormalities in distal segment organization cause a subset of Joubert syndrome cases.
AB - Cilia, essential motile and sensory organelles, have several compartments: the basal body, transition zone, and the middle and distal axoneme segments. The distal segment accommodates key functions, including cilium assembly and sensory activities. While the middle segment contains doublet microtubules (incomplete B-tubules fused to complete A-tubules), the distal segment contains only A-tubule extensions, and its existence requires coordination of microtubule length at the nanometer scale. We show that three conserved proteins, two of which are mutated in the ciliopathy Joubert syndrome, determine the geometry of the distal segment, by controlling the positions of specific microtubule ends. FAP256/CEP104 promotes A-tubule elongation. CHE-12/Crescerin and ARMC9 act as positive and negative regulators of B-tubule length, respectively. We show that defects in the distal segment dimensions are associated with motile and sensory deficiencies of cilia. Our observations suggest that abnormalities in distal segment organization cause a subset of Joubert syndrome cases.
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U2 - 10.1083/jcb.201804141
DO - 10.1083/jcb.201804141
M3 - Article
C2 - 30217954
AN - SCOPUS:85058000429
VL - 217
SP - 4298
EP - 4313
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 12
ER -