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Identification of a neuron-specific human gene, KIAA1110, that is a guanine nucleotide exchange factor for ARF1
Authors:Hattori Yujiro  Ohta Shigeki  Hamada Kenji  Yamada-Okabe Hisafumi  Kanemura Yonehiro  Matsuzaki Yumi  Okano Hideyuki  Kawakami Yutaka  Toda Masahiro
Institution:a Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
b Pharmaceutical Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kanagawa, Japan
c Research Planning and Coordination Department, Gotenba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan
d Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan
e Department of Physiology, Keio University School of Medicine, Tokyo, Japan
f Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
g Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Abstract:To identify neuron-specific genes, we performed gene expression profiling, cDNA microarray and in silico ESTs (expressed sequence tags) analyses. We identified a human neuron-specific gene, KIAA1110 (homologue of rat synArfGEF (Po)), that is a member of the guanine nucleotide exchange factor (GEF) for the ADP-ribosylation factor (ARF). RT-PCR analysis showed that the KIAA1110 gene was expressed specifically in the brain among adult human tissues, whereas no apparent expression was observed in immature neural tissues/cells, such as fetal brain, glioma tissues/cells, and neural stem/precursor cells (NSPCs). The KIAA1110 protein was shown to be expressed in mature neurons but not in undifferentiated NSPCs. Immunohistochemical analysis also showed that KIAA1110 was expressed in neurons of the human adult cerebral cortex. Furthermore, the pull-down assay revealed that KIAA1110 has a GEF activity toward ARF1 that regulates transport along the secretion pathway. These results suggest that KIAA1110 is expressed specifically in mature neurons and may play an important role in the secretion pathway as a GEF for ARF1.
Keywords:ARF–  GEFs  KIAA1110  Neural stem cells
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