Microvillar and ciliary defects in zebrafish lacking an actin-binding bioactive peptide amidating enzyme
| العنوان: | Microvillar and ciliary defects in zebrafish lacking an actin-binding bioactive peptide amidating enzyme |
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| المؤلفون: | Jonathan D. Gitlin, Dhivya Ashok Kumar, Richard E. Mains, Rebecca T. Thomason, Maya Yankova, Stephen M. King, Betty A. Eipper |
| المصدر: | Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, lcsh:Medicine, macromolecular substances, Filamentous actin, Article, Cell Line, Mixed Function Oxygenases, Mice, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, stomatognathic system, Multienzyme Complexes, Ciliogenesis, parasitic diseases, medicine, Animals, Cilia, lcsh:Science, Zebrafish, Actin, Binding Sites, Multidisciplinary, Microvilli, biology, Chemistry, Cilium, Algal Proteins, Chlamydomonas, lcsh:R, Zebrafish Proteins, biology.organism_classification, Actin cytoskeleton, Microvillus, Actins, Cell biology, Trachea, 030104 developmental biology, medicine.anatomical_structure, Gene Knockdown Techniques, embryonic structures, lcsh:Q, 030217 neurology & neurosurgery |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f5e19283ea44b6294019cd476145a11 http://link.springer.com/article/10.1038/s41598-018-22732-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8f5e19283ea44b6294019cd476145a11 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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