Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice. Export

@article{citeulike:3124808, abstract = {Familial macular degeneration is a clinically and genetically heterogeneous group of disorders characterized by progressive central vision loss. Here we show that an R373C missense mutation in the prominin 1 gene (PROM1) causes 3 forms of autosomal-dominant macular degeneration. In transgenic mice expressing R373C mutant human PROM1, both mutant and endogenous PROM1 were found throughout the layers of the photoreceptors, rather than at the base of the photoreceptor outer segments, where PROM1 is normally localized. Moreover, the outer segment disk membranes were greatly overgrown and misoriented, indicating defective disk morphogenesis. Immunoprecipitation studies showed that PROM1 interacted with protocadherin 21 (PCDH21), a photoreceptor-specific cadherin, and with actin filaments, both of which play critical roles in disk membrane morphogenesis. Collectively, our results identify what we believe to be a novel complex involved in photoreceptor disk morphogenesis and indicate a possible role for PROM1 and PCDH21 in macular degeneration.}, address = {Department of Ophthalmology and Visual Science, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah, USA. Center for Human Molecular Biology and Genetics, Sichuan Academy of Medical Sciences, and Sichuan Provincial People's Hospital, Sichuan, People's Republic of China. Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah, USA. Department of Pharmacology and Department of Neurosciences, UCSD School of Medicine, La Jolla, California, USA. Department of Laboratory Medicine and Experimental Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. Institute of Ophthalmology, University College London, London, United Kingdom. Moorfields Eye Hospital, London, United Kingdom. Retina Foundation of the SW and Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Tissue Engineering Laboratories, Biotec, Technical University of Dresden, Dresden, Germany. Institut de Recherche en Ophtalmologie, Sion, Switzerland. Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany. Department of Biology and Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah, USA. Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, California, USA.}, author = {Yang, Zhenglin and Chen, Yali and Lillo, Concepcion and Chien, Jeremy and Yu, Zhengya and Michaelides, Michel and Klein, Martin and Howes, Kim A A. and Li, Yang and Kaminoh, Yuuki and Chen, Haoyu and Zhao, Chao and Chen, Yuhong and Al-Sheikh, Youssef Tawfik T. and Karan, Goutam and Corbeil, Denis and Escher, Pascal and Kamaya, Shin and Li, Chunmei and Johnson, Samantha and Frederick, Jeanne M M. and Zhao, Yu and Wang, Changguan and Cameron, D Joshua J. and Huttner, Wieland B B. and Schorderet, Daniel F F. and Munier, Frances L L. and Moore, Anthony T T. and Birch, David G G. and Baehr, Wolfgang and Hunt, David M M. and Williams, David S S. and Zhang, Kang}, citeulike-article-id = {3124808}, citeulike-linkout-0 = {http://dx.doi.org/10.1172/JCI35891}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18654668}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18654668}, day = {1}, doi = {10.1172/JCI35891}, issn = {0021-9738}, journal = {The Journal of clinical investigation}, keywords = {degeneration, macular, mice, photoreceptor, proml1}, month = {August}, number = {8}, pages = {2908--2916}, posted-at = {2008-08-14 20:49:46}, priority = {2}, title = {Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice.}, url = {http://dx.doi.org/10.1172/JCI35891}, volume = {118}, year = {2008} }

TY - JOUR ID - citeulike:3124808 L3 - citeulike-article-id:3124808 N2 - Familial macular degeneration is a clinically and genetically heterogeneous group of disorders characterized by progressive central vision loss. Here we show that an R373C missense mutation in the prominin 1 gene (PROM1) causes 3 forms of autosomal-dominant macular degeneration. In transgenic mice expressing R373C mutant human PROM1, both mutant and endogenous PROM1 were found throughout the layers of the photoreceptors, rather than at the base of the photoreceptor outer segments, where PROM1 is normally localized. Moreover, the outer segment disk membranes were greatly overgrown and misoriented, indicating defective disk morphogenesis. Immunoprecipitation studies showed that PROM1 interacted with protocadherin 21 (PCDH21), a photoreceptor-specific cadherin, and with actin filaments, both of which play critical roles in disk membrane morphogenesis. Collectively, our results identify what we believe to be a novel complex involved in photoreceptor disk morphogenesis and indicate a possible role for PROM1 and PCDH21 in macular degeneration. IS - 8 JF - The Journal of clinical investigation SN - 0021-9738 AD - Department of Ophthalmology and Visual Science, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah, USA. Center for Human Molecular Biology and Genetics, Sichuan Academy of Medical Sciences, and Sichuan Provincial People's Hospital, Sichuan, People's Republic of China. Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah, USA. Department of Pharmacology and Department of Neurosciences, UCSD School of Medicine, La Jolla, California, USA. Department of Laboratory Medicine and Experimental Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. Institute of Ophthalmology, University College London, London, United Kingdom. Moorfields Eye Hospital, London, United Kingdom. Retina Foundation of the SW and Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Tissue Engineering Laboratories, Biotec, Technical University of Dresden, Dresden, Germany. Institut de Recherche en Ophtalmologie, Sion, Switzerland. Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany. Department of Biology and Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah, USA. Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, California, USA. EP - 2916 TI - Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice. VL - 118 SP - 2908 KW - degeneration KW - macular KW - mice KW - photoreceptor KW - proml1 AU - Yang, Zhenglin AU - Chen, Yali AU - Lillo, Concepcion AU - Chien, Jeremy AU - Yu, Zhengya AU - Michaelides, Michel AU - Klein, Martin AU - Howes, Kim A AU - Li, Yang AU - Kaminoh, Yuuki AU - Chen, Haoyu AU - Zhao, Chao AU - Chen, Yuhong AU - Al-Sheikh, Youssef Tawfik AU - Karan, Goutam AU - Corbeil, Denis AU - Escher, Pascal AU - Kamaya, Shin AU - Li, Chunmei AU - Johnson, Samantha AU - Frederick, Jeanne M AU - Zhao, Yu AU - Wang, Changguan AU - Cameron, D Joshua AU - Huttner, Wieland B AU - Schorderet, Daniel F AU - Munier, Frances L AU - Moore, Anthony T AU - Birch, David G AU - Baehr, Wolfgang AU - Hunt, David M AU - Williams, David S AU - Zhang, Kang PY - 2008/08/01/ UR - http://dx.doi.org/10.1172/JCI35891 ER -