Identification of alternatively spliced Dab1 and Fyn isoforms in pig

BMC Neuroscience

Research Article

Joachim Herz¹  Hans H Bock²  Xuejun Chai³  Michael Frotscher⁴  Ting Lei⁵  Jihong Yuan⁵  Zaiqing Yang⁵  Huan Long⁶ 

[1] Center for Neurosciences, University of Freiburg, Freiburg, Germany;Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, USA;Department of Medicine 2, University Hospital Freiburg, Freiburg, Germany;Center for Neurosciences, University of Freiburg, Freiburg, Germany;Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany;Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany;Center for Neurosciences, University of Freiburg, Freiburg, Germany;Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, 430070, Wuhan, PR China;Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, 430070, Wuhan, PR China;Institute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany;

关键词: Radiation Hybrid;    Nuclear Export Signal;    Dominant Negative Form;    Primary Hippocampal Neuron;    Nucleocytoplasmic Shuttle;   

DOI  :  10.1186/1471-2202-12-17

 received in 2010-11-01, accepted in 2011-02-05,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundDisabled-1 (Dab1) is an adaptor protein that is essential for the intracellular transduction of Reelin signaling, which regulates the migration and differentiation of postmitotic neurons during brain development in vertebrates. Dab1 function depends on its tyrosine phosphorylation by Src family kinases, especially Fyn.ResultsWe have isolated alternatively spliced forms of porcine Dab1 from brain (sDab1) and liver (sDab1-Li) and Fyn from brain (sFyn-B) and spleen (sFyn-T). Radiation hybrid mapping localized porcine Dab1 (sDab1) and Fyn (sFyn) to chromosomes 6q31-35 and 1p13, respectively. Real-time quantitative RT-PCR (qRT-PCR) demonstrated that different isoforms of Dab1 and Fyn have tissue-specific expression patterns, and sDab1 and sFyn-B display similar temporal expression characteristics in the developing porcine cerebral cortex and cerebellum. Both sDab1 isoforms function as nucleocytoplasmic shuttling proteins. It was further shown that sFyn phosphorylates sDab1 at tyrosyl residues (Tyr) 185, 198/200 and 232, whereas sDab1-Li was phosphorylated at Tyr 185 and Tyr 197 (corresponding to Y232 in sDab1) in vitro.ConclusionsAlternative splicing generates natural sDab1-Li that only carries Y185 and Y197 (corresponding to Y232 in sDab1) sites, which can be phosphorylated by Fyn in vitro. sDab1-Li is an isoform that is highly expressed in peripheral organs. Both isoforms are suggested to be nucleocytoplasmic shuttling proteins. Our results imply that the short splice form sDab1-Li might regulate cellular responses to different cell signals by acting as a dominant negative form against the full length sDab1 variant and that both isoforms might serve different signaling functions in different tissues.

【 授权许可】

Unknown   
© Long et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.