Golli Myelin Basic Proteins Modulate Voltage-Operated Ca(++) Influx and Development in Cortical and Hippocampal Neurons.
The golli proteins, products of the myelin basic protein gene, are widely expressed in oligodendrocyte progenitor cells and neurons during the postnatal development of the brain. While golli appears to be important for oligodendrocyte migration and differentiation, its function in neuronal development is completely unknown. We have found that golli proteins function as new and novel modulators of voltage-operated Ca(++) channels (VOCCs) in neurons. In vitro, golli knock-out (KO) neurons exhibit decreased Ca(++) influx after plasma membrane depolarization and a substantial maturational delay. Increased expression of golli proteins enhances L-type Ca(++) entry and processes outgrowth in cortical neurons, and pharmacological activation of L-type Ca(++) channels stimulates maturation and prevents cell death in golli-KO neurons. In situ, Ca(++) influx mediated by L-type VOCCs was significantly decreased in cortical and hippocampal neurons of the golli-KO brain. These Ca(++) alterations affect cortical and hippocampal development and the proliferation and survival of neural progenitor cells during the postnatal development of the golli-KO brain. The CA1/3 sections and the dentate gyrus of the hippocampus were reduced in the golli-KO mice as well as the density of dendrites in the somatosensory cortex. Furthermore, the golli-KO mice display abnormal behavior including deficits in episodic memory and reduced anxiety. Because of the expression of the golli proteins within neurons in learning and memory centers of the brain, this work has profound implication in neurodegenerative diseases and neurological disorders.
Hunter James Kelly Research Institute, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, SUNY, University at Buffalo, NYS Center of Excellence, 701 Ellicott St., Buffalo, NY, 14203, USA.
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Hunter James Kelly Research Institute, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, SUNY, University at Buffalo, NYS Center of Excellence, 701 Ellicott St., Buffalo, NY, 14203, USA.
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Santiago González
Hunter James Kelly Research Institute, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, SUNY, University at Buffalo, NYS Center of Excellence, 701 Ellicott St., Buffalo, NY, 14203, USA.
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Spreuer
Semel Institute for Neuroscience and Human Behavior, Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Neuroscience Research Building, 635 Charles Young Drive, Los Angeles, CA, 90095, USA.
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Handley
Semel Institute for Neuroscience and Human Behavior, Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, UCLA, Neuroscience Research Building, 635 Charles Young Drive, Los Angeles, CA, 90095, USA.
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Campagnoni
Hunter James Kelly Research Institute, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, SUNY, University at Buffalo, NYS Center of Excellence, 701 Ellicott St., Buffalo, NY, 14203, USA. ppaez@buffalo.edu.
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Paez
D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D006624:Hippocampus / Q000166:cytology*; D018345:Mice, Knockout; D009043:Motor Activity; D004676:Myelin Basic Protein / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*
D015220:Calcium Channels; D004676:Myelin Basic Protein; D002118:Calcium
Brain development; Calcium influx; Golli-MBP; Neuron development; Voltage-operated Ca++ channels