Tropomodulin 1 Regulation of Actin Is Required for the Formation of Large Paddle Protrusions Between Mature Lens Fiber Cells
| Autor: | Velia M. Fowler, Roberta B. Nowak, Sondip K. Biswas, Paul G. FitzGerald, Catherine Cheng, Woo-Kuen Lo |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytoskeleton organization DNA Mutational Analysis Inbred C57BL Ophthalmology & Optometry Medical and Health Sciences Cell membrane Lens Mice Scanning Cells Cultured Mice Knockout Microscopy actinin Cultured paddles biology Cell Differentiation Anatomy Biological Sciences eye Lens Fiber Actin Cytoskeleton medicine.anatomical_structure Lens (anatomy) Tropomodulin Cells Knockout macromolecular substances Electron Cataract 03 medical and health sciences Lens Crystalline medicine Animals Actin Crystalline Animal DNA Actin cytoskeleton Actins Mice Inbred C57BL Disease Models Animal 030104 developmental biology spectrin Fimbrin Disease Models Mutation Microscopy Electron Scanning Biophysics biology.protein interdigitations |
| Zdroj: | Investigative ophthalmology & visual science, vol 57, iss 10 |
| Popis: | Author(s): Cheng, Catherine; Nowak, Roberta B; Biswas, Sondip K; Lo, Woo-Kuen; FitzGerald, Paul G; Fowler, Velia M | Abstract: PurposeTo elucidate the proteins required for specialized small interlocking protrusions and large paddle domains at lens fiber cell tricellular junctions (vertices), we developed a novel method to immunostain single lens fibers and studied changes in cell morphology due to loss of tropomodulin 1 (Tmod1), an F-actin pointed end-capping protein.MethodsWe investigated F-actin and F-actin-binding protein localization in interdigitations of Tmod1+/+ and Tmod1-/- single mature lens fibers.ResultsF-actin-rich small protrusions and large paddles were present along cell vertices of Tmod1+/+ mature fibers. In contrast, Tmod1-/- mature fiber cells lack normal paddle domains, while small protrusions were unaffected. In Tmod1+/+ mature fibers, Tmod1, β2-spectrin, and α-actinin are localized in large puncta in valleys between paddles; but in Tmod1-/- mature fibers, β2-spectrin was dispersed while α-actinin was redistributed at the base of small protrusions and rudimentary paddles. Fimbrin and Arp3 (actin-related protein 3) were located in puncta at the base of small protrusions, while N-cadherin and ezrin outlined the cell membrane in both Tmod1+/+ and Tmod1-/- mature fibers.ConclusionsThese results suggest that distinct F-actin organizations are present in small protrusions versus large paddles. Formation and/or maintenance of large paddle domains depends on a β2-spectrin-actin network stabilized by Tmod1. α-Actinin-crosslinked F-actin bundles are enhanced in absence of Tmod1, indicating altered cytoskeleton organization. Formation of small protrusions is likely facilitated by Arp3-branched and fimbrin-bundled F-actin networks, which do not depend on Tmod1. This is the first work to reveal the F-actin-associated proteins required for the formation of paddles between lens fibers. |
| Databáze: | OpenAIRE |
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