A bioactive peptide amidating enzyme is required for ciliogenesis
- University of Connecticut Health Center, United States
- University of California Los Angeles, United States
- University of California, Los Angeles, United States
Abstract
The pathways controlling cilium biogenesis in different cell types have not been fully elucidated. We recently identified peptidylglycine α-amidating monooxygenase (PAM), an enzyme required for generating amidated bioactive signaling peptides, in Chlamydomonas and mammalian cilia. Here, we show that PAM is required for the normal assembly of motile and primary cilia in Chlamydomonas, planaria and mice. Chlamydomonas PAM knockdown lines failed to assemble cilia beyond the transition zone, had abnormal Golgi architecture and altered levels of cilia assembly components. Decreased PAM gene expression reduced motile ciliary density on the ventral surface of planaria and resulted in the appearance of cytosolic axonemes lacking a ciliary membrane. The architecture of primary cilia on neuroepithelial cells in Pam-/- mouse embryos was also aberrant. Our data suggest that PAM activity and alterations in post-Golgi trafficking contribute to the observed ciliogenesis defects and provide an unanticipated, highly conserved, link between PAM, amidation and ciliary assembly.
Article and author information
Author details
Funding
National Institutes of Health (DK032949)
- Betty A Eipper
National Institutes of Health (GM051293)
- Stephen M King
National Institutes of Health (GM042143)
- Sabeeha S Merchant
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Anna Akhmanova, Utrecht University, Netherlands
Ethics
Animal experimentation: All procedures involving mice were approved by the UCHC Institutional Animal Care and Use Committee (protocol 101529-1119), in accordance with National Institutes of Health and ARRIVE guidelines (https://www. nc3rs.org.uk/arrive-guidelines).
Version history
- Received: February 3, 2017
- Accepted: May 15, 2017
- Accepted Manuscript published: May 17, 2017 (version 1)
- Version of Record published: June 6, 2017 (version 2)
- Version of Record updated: June 16, 2017 (version 3)
Copyright
© 2017, Kumar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A bioactive peptide amidating enzyme is required for ciliogenesis
eLife 6:e25728.
https://doi.org/10.7554/eLife.25728
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