LANCL2 is necessary for abscisic acid binding and signaling in human granulocytes and in rat insulinoma cells.
Abscisic acid (ABA) is a plant hormone regulating fundamental physiological functions in plants, such as response to abiotic stress. Recently, ABA was shown to be produced and released by human granulocytes, by insulin-producing rat insulinoma cells, and by human and murine pancreatic beta cells. ABA autocrinally stimulates the functional activities specific for each cell type through a receptor-operated signal transduction pathway, sequentially involving a pertussis toxin-sensitive receptor/G-protein complex, cAMP, CD38-produced cADP-ribose and intracellular calcium. Here we show that the lanthionine synthetase C-like protein LANCL2 is required for ABA binding on the membrane of human granulocytes and that LANCL2 is necessary for transduction of the ABA signal into the cell-specific functional responses in granulocytes and in rat insulinoma cells. Co-expression of LANCL2 and CD38 in the human HeLa cell line reproduces the ABA-signaling pathway. Results obtained with granulocytes and CD38(+)/LANCL2(+) HeLa transfected with a chimeric G-protein (G alpha(q/i)) suggest that the pertussis toxin-sensitive G-protein coupled to LANCL2 is a G(i). Identification of LANCL2 as a critical component of the ABA-sensing protein complex will enable the screening of synthetic ABA antagonists as prospective new anti-inflammatory and anti-diabetic agents.
Sturla
Laura
L
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132.
Fresia
Chiara
C
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132.
Guida
Lucrezia
L
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132.
Bruzzone
Santina
S
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132.
Scarfì
Sonia
S
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132; Advanced Biotechnology Center, Largo R. Benzi 10, Genova 16132.
Usai
Cesare
C
Institute of Biophysics, National Research Council, Via De Marini 6, Genova 16149.
Fruscione
Floriana
F
Advanced Biotechnology Center, Largo R. Benzi 10, Genova 16132.
Magnone
Mirko
M
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132.
Millo
Enrico
E
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132.
Basile
Giovanna
G
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132.
Grozio
Alessia
A
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132.
Jacchetti
Emanuela
E
Institute of Biophysics, National Research Council, Via De Marini 6, Genova 16149.
Allegretti
Marcello
M
Dompé Pha.r.ma, Località Campo di Pile 1, L'Aquila 67100, Italy.
De Flora
Antonio
A
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132. Electronic address: toninodf@unige.it.
Zocchi
Elena
E
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 1, Genova 16132; Advanced Biotechnology Center, Largo R. Benzi 10, Genova 16132. Electronic address: ezocchi@unige.it.
D000040:Abscisic Acid / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D028044:Phosphate-Binding Proteins; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
C471704:LANCL2 protein, human; C544683:LANCL2 protein, rat; D008565:Membrane Proteins; D009687:Nuclear Proteins; D028044:Phosphate-Binding Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000040:Abscisic Acid; C090939:GDP-ribosyl cyclase; D009699:N-Glycosyl Hydrolases