A novel member of the leucine-rich repeat superfamily induced in rat astrocytes by beta-amyloid.
beta-Amyloid (Abeta) deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease (AD). Although the molecular mechanisms by which Abeta contributes to the progression of neuropathologic changes have not been established entirely, there is little doubt that the association of Abeta with astrocytes, the predominant cell type in brain, has significant influence on exacerbation of the disease. In an effort to identify key molecules involved in AD, we investigated Abeta-responsive genes using rat astrocytes. In this study, we identified a novel Abeta-induced rat gene, designated as Lib, encoding a type I transmembrane protein with an extracellular domain that contains fifteen leucine-rich repeats (LRRs). Human counterpart of rat Lib is located on chromosome 3q29 and human Lib mRNA found in particularly placenta. Lib mRNA levels in rat C6 astrocytoma cells can be increased by pro-inflammatory cytokines and the rat Lib-transfected cells express Lib protein on the cell surfaces. Lib appears to be a member of the LRR superfamily which is involved in cell-cell and/or -extracellular matrix interactions including adhesion or target recognition in neuroinflammatory states.
Satoh
Kazuki
K
Discovery Research Laboratory, Daiichi Pharmaceutical Company, Ltd., Tokyo R&D Center, 1-16-13 Kitakasai, Edogawa-Ku, Tokyo, 134-8630, Japan. satohj7i@daiichipharm.co.jp
Hata
Mitsumi
M
Yokota
Hiroshi
H
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D015723:Gene Library; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009928:Organ Specificity; D010920:Placenta / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; C446297:LRRC15 protein, human; C486719:Lrrc15 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma