Identification and characterization of a truncated isoform of NELL2.
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.
Kim
Dong-Gyu
DG
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.
Hwang
Eun Mi
EM
Yoo
Jae Cheal
JC
Kim
Eunju
E
Park
Nammi
N
Rhee
Sangmyung
S
Ha
Chang Man
CM
Hong
Seong-Geun
SG
Park
Jae-Yong
JY
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D018388:Codon, Terminator / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics; D017434:Protein Structure, Tertiary; D051381:Rats
D018388:Codon, Terminator; D006023:Glycoproteins; C104145:NELL2 protein, human; D009419:Nerve Tissue Proteins; D021382:Protein Sorting Signals