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Identification and characterization of a truncated isoform of NELL2
Authors:Dong-Gyu Kim  Eun Mi Hwang  Jae Cheal Yoo  Nammi Park  Chang Man Ha  Jae-Yong Park
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
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.
Keywords:NELL2  Truncated NELL2  Alternative splicing  Neurite outgrowth  Secretion
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