Keratins and Plakin family cytolinker proteins control the length of epithelial microridge protrusions
| العنوان: | Keratins and Plakin family cytolinker proteins control the length of epithelial microridge protrusions |
|---|---|
| المؤلفون: | Aaron P. van Loon, Lamia Saiyara Choudhury, Yasuko Inaba, Alvaro Sagasti, Vasudha Chauhan |
| المصدر: | eLife, Vol 9 (2020) eLife |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Intermediate Filaments, Plakin, Cell membrane, protrusion, 0302 clinical medicine, Keratin, Biology (General), Cytoskeleton, Intermediate filament, keratin, Periplakin, Zebrafish, Skin, chemistry.chemical_classification, integumentary system, Chemistry, General Neuroscience, General Medicine, Cell biology, medicine.anatomical_structure, Keratins, Medicine, actin, Research Article, QH301-705.5, Science, Morphogenesis, morphogenesis, macromolecular substances, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Microtubule, medicine, Animals, Protein Precursors, Actin, General Immunology and Microbiology, Plakins, Membrane Proteins, Epithelial Cells, Cell Biology, Zebrafish Proteins, 030104 developmental biology, Biophysics, Cell Surface Extensions, microridge, 030217 neurology & neurosurgery, Developmental Biology |
| الوصف: | Actin filaments and microtubules create diverse cellular protrusions, but intermediate filaments, the strongest and most stable cytoskeletal elements, are not known to directly participate in the formation of protrusions. Here we show that keratin intermediate filaments directly regulate the morphogenesis of microridges, elongated protrusions arranged in elaborate maze-like patterns on the surface of mucosal epithelial cells. We found that microridges on zebrafish skin cells contained both actin and keratin filaments. Keratin filaments stabilized microridges, and overexpressing keratins lengthened them. Envoplakin and periplakin, plakin family cytolinkers that bind F-actin and keratins, localized to microridges, and were required for their morphogenesis. Strikingly, plakin protein levels directly dictate microridge length. An actin-binding domain of periplakin was required to initiate microridge morphogenesis, whereas periplakin-keratin binding was required to elongate microridges. These findings separate microridge morphogenesis into distinct steps, expand our understanding of intermediate filament functions, and identify microridges as protrusions that integrate actin and intermediate filaments. eLife digest Cells adopt a wide array of irregular and bumpy shapes, which are scaffolded by an internal structure called the cytoskeleton. This network of filaments can deform the cell membrane the way tent poles frame a canvas. Cells contain three types of cytoskeleton elements (actin filaments, intermediate filaments, and microtubules), each with unique chemical and mechanical properties. One of the main roles of the cytoskeleton is to create protrusions, a range of structures that ‘stick out’ of a cell to allow movement and interactions with the environment. Both actin filaments and microtubules help form protrusions, but the role of intermediate filaments remains unclear. Microridges are a type of protrusion found on cells covered by mucus, for instance on the surface of the eye, inside the mouth, or on fish skin. These small bumps are organised on the membrane of a cell in fingerprint-like arrangements. Scientists know that actin networks are necessary for microridges to form; yet, many structures supported by actin filaments are not stable over time, suggesting that another component of the cytoskeleton might be lending support. Intermediate filaments are the strongest, most stable type of cytoskeleton element, and they can connect to actin filaments via linker proteins. However, research has yet to show that this kind of cooperation happens in any membrane protrusion. Here, Inaba et al. used high-resolution microscopy to monitor microridge development in the skin of live fish. In particular, they focused on a type of intermediate filaments known as keratin filaments. This revealed that, inside microridges, the keratin and actin networks form alongside each other, with linker proteins called Envoplakin and Periplakin connecting the two structures together. Genetic experiments revealed that Envoplakin and Periplakin must attach to actin for microridges to start forming. However, the two proteins bind to keratin for protrusions to grow. This work therefore highlights how intermediate filaments and linker proteins contribute to the formation of these structures. Many tissues must be covered in mucus to remain moist and healthy. As microridges likely contribute to mucus retention, the findings by Inaba et al. may help to better understand how disorders linked to problems in mucus emerge. |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b52d9a82e2f8d67ec555442b3cc6969 https://doi.org/10.1101/2020.02.18.954933 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5b52d9a82e2f8d67ec555442b3cc6969 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |