title: Regulation of retinoschisin secretion in Weri-Rb1 cells by the F-actin and microtubule cytoskeleton.
abstract: Retinoschisin is encoded by the gene responsible for X-linked retinoschisis (XLRS), an early onset macular degeneration that results in a splitting of the inner layers of the retina and severe loss in vision. Retinoschisin is predominantly expressed and secreted from photoreceptor cells as a homo-oligomer protein; it then associates with the surface of retinal cells and maintains the retina cellular architecture. Many missense mutations in the XLRS1 gene are known to cause intracellular retention of retinoschisin, indicating that the secretion process of the protein is a critical step for its normal function in the retina. However, the molecular mechanisms underlying retinoschisin's secretion remain to be fully elucidated. In this study, we investigated the role of the F-actin cytoskeleton in the secretion of retinoschisin by treating Weri-Rb1 cells, which are known to secrete retinoschisin, with cytochalasin D, jasplakinolide, Y-27632, and dibutyryl cGMP. Our results show that cytochalasin D and jasplakinolide inhibit retinoschisin secretion, whereas Y-27632 and dibutyryl cGMP enhance secretion causing F-actin alterations. We also demonstrate that high concentrations of taxol, which hyperpolymerizes microtubules, inhibit retinoschisin secretion. Our data suggest that retinoschisin secretion is regulated by the F-actin cytoskeleton, that cGMP or inhibition of ROCK alters F-actin structure enhancing the secretion, and that the microtubule cytoskeleton is also involved in this process.
authors: Jules Stein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Eiko
authors: E
authors: Kitamura
authors: Yekaterina E
authors: YE
authors: Gribanova
authors: Debora B
authors: DB
authors: Farber
mesh_terms: D000199:Actins / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D047630:Depsipeptides / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D041441:Retinoschisis / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000199:Actins; D000577:Amides; D047630:Depsipeptides; D005136:Eye Proteins; D011725:Pyridines; C108726:RS1 protein, human; D050257:Tubulin Modulators; C057531:jasplakinolide; C108830:Y 27632; D015638:Cytochalasin D; D003995:Dibutyryl Cyclic GMP; D017239:Paclitaxel