Gamma synuclein: subcellular localization in neuronal and non-neuronal cells and effect on signal transduction.
Synucleins are small, highly conserved proteins in vertebrates, especially abundant in neurons and typically enriched in presynaptic terminals. alpha-Synuclein protein and a fragment of it, called NAC, have been found in association with pathological lesions of neurodegenerative diseases. Recently, mutations in a alpha-synuclein gene have been reported in families susceptible to an inherited form of Parkinson's diseases. In addition, alpha-synuclein has been implicated in the pathophysiology of other neurodegenerative diseases, including Alzheimer's disease and multiple system atrophy. Far less is known about other members of the synuclein family, beta- and gamma-synucleins. gamma-synuclein is up-regulated in several types of cancer and may affect the integrity of the neurofilament network, while its bovine ortholog, synoretin, activates the Elk-1 signal transduction pathway. In this paper, we present data about the localization and properties of human and bovine gamma-synuclein in several neuronal and non-neuronal cell cultures derived from ocular tissues. We show that gamma-synuclein is present in the perinuclear area and is localized to centrosomes in several types of human interphase cells and in bovine retinal pigment epithelium. In mitotic cells, gamma-synuclein staining is localized to the poles of the spindle. Further, overexpression of synoretin in retinoblastoma cells up-regulates MAPK and Elk-1. These results support the view that gamma-synuclein is a centrosome protein that may be involved in signal transduction pathways.
Surguchov
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Department of Ophthalmology and Visual Sciences, Washington University, St. Louis, Missouri 63110, USA. surguchov@vision.wustl.edu
Palazzo
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Surgucheva
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I
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002417:Cattle; D018385:Centrosome / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D036143:Receptor, EphA8; D012160:Retina / Q000166:cytology; D012175:Retinoblastoma / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D008941:Spindle Apparatus; D013347:Subcellular Fractions; D051843:Synucleins; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051844:alpha-Synuclein; D051845:gamma-Synuclein
D005136:Eye Proteins; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D051845:gamma-Synuclein; D020794:Receptor Protein-Tyrosine Kinases; D036143:Receptor, EphA8; D020928:Mitogen-Activated Protein Kinases