Identification and characterization of a truncated isoform of NELL2 |
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Authors: | Dong-Gyu Kim Eun Mi Hwang Jae Cheal Yoo Nammi Park Chang Man Ha Jae-Yong Park |
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Institution: | a Department of Physiology, Institute of Health Science and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, 90 Chilam-Dong, Jinju 660-751, South Korea b Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, South Korea c Department of Pharmacology and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, South Korea |
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Abstract: | NELL2 is a neuron-specific secreted glycoprotein containing an N-terminal thrombospondin I-like domain (TSP-N). In this study, we describe NELL2-Tsp, a novel alternative splice variant of rat NELL2. NELL2-Tsp uses an alternate stop codon resulting in a C-terminal truncated form of NELL2, containing a signal peptide and a TSP-N domain. NELL2-Tsp is a glycosylated protein specifically expressed in brain tissue. NELL2-Tsp and NELL2 are secreted, likely due to the putative signal peptide. However, due to the truncation, the secreted portion of NELL2-Tsp is smaller than that of NELL2. Immunoprecipitation analysis confirmed that NELL2-Tsp was able to associate with NELL2 and with itself. In addition, expression of NELL2-Tsp notably reduced secretion of NELL2 and inhibited NELL2-mediated neurite outgrowth. These results suggest that NELL2-Tsp may act as a negative regulator of wild-type NELL2. |
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Keywords: | NELL2 Truncated NELL2 Alternative splicing Neurite outgrowth Secretion |
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