The adhesion-GPCR BAI3, a gene linked to psychiatric disorders, regulates dendrite morphogenesis in neurons

• Published in: Molecular psychiatry Vol. 18; no. 8; pp. 943 - 950
• Main Authors: LANOUE, V, USARDI, A, SIGOILLOT, S. M, TALLEUR, M, IYER, K, MARIANI, J, ISOPE, P, VODJDANI, G, HEINTZ, N, SELIMI, F
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.08.2013
• Subjects: Actin; Adaptor Proteins, Signal Transducing - metabolism; Adult and adolescent clinical studies; Amino acids; Angiogenesis; Animals; Autism; Biological and medical sciences; Biology; Brain diseases; Brain research; Cell adhesion; Cells, Cultured; Dendrites - physiology; Dendrites - ultrastructure; Gene Knockdown Techniques; Genetic aspects; Genetic regulation; Interdisciplinary aspects; Lentivirus; Life Sciences; Medical sciences; Membrane Proteins; Mental disorders; Mental illness; Mice; Mice, Transgenic; Miscellaneous; Morphogenesis; Mutation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Nervous system; Neurogenesis - genetics; Neurogenesis - physiology; Neurons; Original; Physiological aspects; Proteins; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Purkinje Cells - physiology; Purkinje Cells - ultrastructure; Schizophrenia; Signal Transduction - physiology; France; United States > US; Paris France; Animal model; Rodentia; Purkinje neuron; Transgenic animal; Genetic determinism; Adhesion; Dendrite; Morphogenesis; Vertebrata; Mammalia; Mouse; G protein coupled receptor; Animal; BAI3; Mental disorder; ELMO1; Genetics; adhesion-GPCR; Purkinje cell; dendrite; morphogenesis
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2013.46

Adhesion-G protein-coupled receptors (GPCRs) are a poorly studied subgroup of the GPCRs, which have diverse biological roles and are major targets for therapeutic intervention. Among them, the Brain Angiogenesis Inhibitor (BAI) family has been linked to several psychiatric disorders, but despite their very high neuronal expression, the function of these receptors in the central nervous system has barely been analyzed. Our results, obtained using expression knockdown and overexpression experiments, reveal that the BAI3 receptor controls dendritic arborization growth and branching in cultured neurons. This role is confirmed in Purkinje cells in vivo using specific expression of a deficient BAI3 protein in transgenic mice, as well as lentivirus driven knockdown of BAI3 expression. Regulation of dendrite morphogenesis by BAI3 involves activation of the RhoGTPase Rac1 and the binding to a functional ELMO1, a critical Rac1 regulator. Thus, activation of the BAI3 signaling pathway could lead to direct reorganization of the actin cytoskeleton through RhoGTPase signaling in neurons. Given the direct link between RhoGTPase/actin signaling pathways, neuronal morphogenesis and psychiatric disorders, our mechanistic data show the importance of further studying the role of the BAI adhesion-GPCRs to understand the pathophysiology of such brain diseases.