title: LUMAN/CREB3 is a key regulator of glucocorticoid-mediated stress responses.
abstract: Altered glucocorticoid sensitivity is believed to contribute to a number of human diseases, including inflammatory and autoimmune conditions as well as disorders characterized by abnormal hypothalamic-pituitary-adrenal axis (HPA) function. LUMAN (or CREB3), originally identified through its interaction with a cell cycle regulator HCFC1, is an endoplasmic reticulum membrane-bound transcription factor that is involved in the unfolded protein response. Here we demonstrate that LUMAN changes the glucocorticoid response by modulating the expression of the glucocorticoid receptor leading to an overall increase in GR activity. Luman-deficient mice exhibited a blunted stress response characterized by low levels of both anxiety and depressive-like behaviour in addition to low circulating corticosterone levels. These mice also have reduced dendritic branching in the CA3 region of the hippocampus, consistent with increased GR responses. These findings are consistent with the notion that elevated GR activities are the primary cause of the observed phenotype in these LUMAN-deficient mice. We thus postulate that LUMAN is a key regulator of GR-mediated signaling and modulates HPA axis reactivity.
authors: Department of Molecular and Cellular Biology, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada.
authors: Jenna
authors: J
authors: Penney
authors: Department of Biomedical Sciences, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada.
authors: Ari
authors: A
authors: Mendell
authors: Department of Molecular and Cellular Biology, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada.
authors: Minghua
authors: M
authors: Zeng
authors: Department of Biomedical Sciences, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada.
authors: Khoa
authors: K
authors: Tran
authors: Department of Psychology, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada.
authors: Jennifer
authors: J
authors: Lymer
authors: Department of Pathobiology, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada.
authors: Patricia V
authors: PV
authors: Turner
authors: Department of Psychology, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada.
authors: Elena
authors: E
authors: Choleris
authors: Department of Biomedical Sciences, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada.
authors: Neil
authors: N
authors: MacLusky
authors: Department of Molecular and Cellular Biology, University of Guelph, 488 Gordon Street, Guelph, Ontario, N1G 2W1, Canada. Electronic address: rlu@uoguelph.ca.
authors: Ray
authors: R
authors: Lu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D056654:CA3 Region, Hippocampal / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D016019:Survival Analysis
chemical_list: C116472:Creb3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003345:Corticosterone
keywords: Glucocorticoid receptor; Hippocampus; Hypothalamic pituitary adrenal axis; LUMAN/CREB3; Stress