Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, United States
Daniela Strenkert
Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, United States
Ramila S Patel-King
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, United States
Michael T Leonard
Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, United States
Sabeeha S Merchant
Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, United States; Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, United States
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, United States; Department of Neuroscience, University of Connecticut Health Center, Farmington, United States
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.
