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Cell Mol Life Sci. 2019 Jun;76(12):2329-2348. doi: 10.1007/s00018-019-03065-w. Epub 2019 Mar 16.

Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis.

Author information

1
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA.
2
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, 94158, USA.
3
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, 06030, USA.
4
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA. king@uchc.edu.

Abstract

Many secreted peptides used for cell-cell communication require conversion of a C-terminal glycine to an amide for bioactivity. This reaction is catalyzed only by the integral membrane protein peptidylglycine α-amidating monooxygenase (PAM). PAM has been highly conserved and is found throughout the metazoa; PAM-like sequences are also present in choanoflagellates, filastereans, unicellular and colonial chlorophyte green algae, dinoflagellates and haptophytes. Recent studies have revealed that in addition to playing a key role in peptidergic signaling, PAM also regulates ciliogenesis in vertebrates, planaria and chlorophyte algae, and is required for the stability of actin-based microvilli. Here we briefly introduce the basic principles involved in ciliogenesis, the sequential reactions catalyzed by PAM and the trafficking of PAM through the secretory and endocytic pathways. We then discuss the multi-faceted roles this enzyme plays in the formation and maintenance of cytoskeleton-based cellular protrusions and propose models for how PAM protein and amidating activity might contribute to ciliogenesis. Finally, we consider why some ciliated organisms lack PAM, and discuss the potential ramifications of ciliary localized PAM for the endocrine features commonly observed in patients with ciliopathies.

KEYWORDS:

Actin; Amidation; Chlamydomonas; Cilia; Microvilli; Peptidylglycine α-amidating monooxygenase

PMID:
30879092
PMCID:
PMC6529398
DOI:
10.1007/s00018-019-03065-w
[Indexed for MEDLINE]
Free PMC Article

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