Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity

Journal of Cell Science
Dhivya KumarB A Eipper

Abstract

Ciliary axonemes and basal bodies were present in the last eukaryotic common ancestor and play crucial roles in sensing and responding to environmental cues. Peptidergic signaling, generally considered a metazoan innovation, is essential for organismal development and homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) is crucial for the last step of bioactive peptide biosynthesis. However, identification of a complete PAM-like gene in green algal genomes suggests ancient evolutionary roots for bioactive peptide signaling. We demonstrate that the Chlamydomonas reinhardtii PAM gene encodes an active peptide-amidating enzyme (CrPAM) that shares key structural and functional features with the mammalian enzyme, indicating that components of the peptide biosynthetic pathway predate multicellularity. In addition to its secretory pathway localization, CrPAM localizes to cilia and tightly associates with the axonemal superstructure, revealing a new axonemal enzyme activity. This localization pattern is conserved in mammals, with PAM present in both motile and immotile sensory cilia. The conserved ciliary localization of PAM adds to the known signaling capabilities of the eukaryotic cilium and provides a potential mechanistic l...Continue Reading

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Citations

Dec 17, 2015·Journal of Molecular Endocrinology·Dhivya KumarBetty A Eipper
May 18, 2017·ELife·Dhivya KumarBetty A Eipper
Dec 7, 2019·PLoS Biology·Raj LuxmiBetty A Eipper
Mar 18, 2019·Cellular and Molecular Life Sciences : CMLS·Dhivya KumarStephen M King
Feb 9, 2021·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Gáspár Jékely
Aug 18, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Sabeeha S MerchantCrysten E Blaby-Haas
Jun 6, 2021·The FEBS Journal·Nils BäckBetty A Eipper

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