A bioactive peptide amidating enzyme is required for ciliogenesis

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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.

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Dhivya Kumar

Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3737-014X
Daniela Strenkert

Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Ramila S Patel-King

Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, United States

Competing interests
The authors declare that no competing interests exist.
Michael T Leonard

Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Sabeeha S Merchant

Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Richard E Mains

Department of Neuroscience, University of Connecticut Health Center, Farmington, United States

Competing interests
The authors declare that no competing interests exist.
Stephen M King

Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, United States

For correspondence
king@uchc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5484-5530
Betty A Eipper

Department of Neuroscience, University of Connecticut Health Center, Farmington, United States

For correspondence
eipper@uchc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1171-5557

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.

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).

Copyright

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.