Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin
| العنوان: | Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin |
|---|---|
| المؤلفون: | Ann Hedley, Cord Brakebusch, Benjamin J. Tyrrell, William Clark, Karthic Swaminathan, Emma F. Woodham, Nikki R. Paul, Klaus M. Hahn, Daniel J. Marston, Heather J. Spence, Robert H. Insall, Stephen W.G. Tait, Evangelos Giampazolias, Laura M. Machesky, Lionel Larue, Michelle R. Scribner, Frieda Kage |
| المساهمون: | Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. |
| المصدر: | Woodham, E F, Paul, N R, Tyrrell, B, Spence, H J, Swaminathan, K, Scribner, M R, Giampazolias, E, Hedley, A, Clark, W, Kage, F, Marston, D J, Hahn, K M, Tait, S W G, Larue, L, Brakebusch, C H, Insall, R H & Machesky, L M 2017, ' Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin ', Current biology : CB, vol. 27, no. 5, pp. 624-637 . https://doi.org/10.1016/j.cub.2017.01.033Test Current Biology |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, rac1 GTP-Binding Protein, rho GTP-Binding Proteins, RHOA, actin cytoskeleton, melanocyte, integrin, Motility, myosin, macromolecular substances, Biology, cell motility, migration, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Mice, Cell Movement, Melanoblast, Rho GTPases, Cell Adhesion, Journal Article, Animals, Cell Lineage, Cdc42, cdc42 GTP-Binding Protein, Actin, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), Neuropeptides, Neural crest, Anatomy, Actins, 3. Good health, Cell biology, adhesion, 030104 developmental biology, Formins, biology.protein, Melanocytes, Pseudopodia, General Agricultural and Biological Sciences, rhoA GTP-Binding Protein, actin, Cytokinesis |
| الوصف: | Summary The individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics. Graphical Abstract Highlights • Loss of Cdc42 in the melanocyte lineage causes pigmentation defects in mice • Cdc42 null melanoblasts are elongated, with severe motility and proliferation defects • Cdc42 and Rac1 have distinct roles for in vivo migration • Cdc42 coordinates actin dynamics, active myosin-II, and integrin-based adhesion Woodham and Paul et al. describe an important role for the small GTPase Cdc42 in cell proliferation and migration in mouse embryo melanoblasts. Loss of Cdc42 leads to severe pigmentation defects, and reveals Cdc42 as a coordinator of multiple cell-migration systems in the melanocyte lineage, including actin, contractility, and adhesion. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0960-9822 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::390ebb21de3ad20200fac1f765e8375cTest https://curis.ku.dk/portal/da/publications/coordination-by-cdc42-of-actin-contractility-and-adhesion-for-melanoblast-movement-in-mouse-skinTest(4d22dbbb-75b4-4e58-9827-584ed70d076c).html |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....390ebb21de3ad20200fac1f765e8375c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09609822 |
|---|