Microvillar and ciliary defects in zebrafish lacking an actin-binding bioactive peptide amidating enzyme
Thomason, Rebecca T.
Gitlin, Jonathan D.
Mains, Richard E.
Eipper, Betty A.
King, Stephen M.
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The assembly of membranous extensions such as microvilli and cilia in polarized cells is a tightly regulated, yet poorly understood, process. Peptidylglycine α-amidating monooxygenase (PAM), a membrane enzyme essential for the synthesis of amidated bioactive peptides, was recently identified in motile and non-motile (primary) cilia and has an essential role in ciliogenesis in Chlamydomonas, Schmidtea and mouse. In mammalian cells, changes in PAM levels alter secretion and organization of the actin cytoskeleton. Here we show that lack of Pam in zebrafish recapitulates the lethal edematous phenotype observed in Pam−/− mice and reveals additional defects. The pam−/− zebrafish embryos display an initial striking loss of microvilli and subsequently impaired ciliogenesis in the pronephros. In multiciliated mouse tracheal epithelial cells, vesicular PAM staining colocalizes with apical actin, below the microvilli. In PAM-deficient Chlamydomonas, the actin cytoskeleton is dramatically reorganized, and expression of an actin paralogue is upregulated. Biochemical assays reveal that the cytosolic PAM C-terminal domain interacts directly with filamentous actin but does not alter the rate of actin polymerization or disassembly. Our results point to a critical role for PAM in organizing the actin cytoskeleton during development, which could in turn impact both microvillus formation and ciliogenesis.
© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 8 (2018): 4547, doi:10.1038/s41598-018-22732-9.
Suggested CitationArticle: Kumar, Dhivya, Thomason, Rebecca T., Yankova, Maya, Gitlin, Jonathan D., Mains, Richard E., Eipper, Betty A., King, Stephen M., "Microvillar and ciliary defects in zebrafish lacking an actin-binding bioactive peptide amidating enzyme", Scientific Reports 8 (2018): 4547, DOI:10.1038/s41598-018-22732-9, https://hdl.handle.net/1912/9644
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