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 ass ociation with pathological lesions of neurodegenerative diseases. Recently. mutations in a alpha -synuclein gene have been reported in families suscep tible to an inherited form of Parkinson's diseases. In addition. alpha -syn uclein has been implicated in the pathophysiology of other neurodegenerativ e 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 an d may affect the integrity of the neurofilament network. while its bovine o rtholog. synoretin, activates the Elk-1 signal transduction pathway. In thi s 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 t he perinuclear area and is localized to centrosomes in several types of hum an interphase cells and in bovine retinal pigment epithelium. In mitotic ce lls, gamma -synuclein staining is localized to the poles of the spindle. Fu rther. overexpression of synoretin in retinoblastoma cells up-regulates MAP K and Elk-1. These results support the view that gamma -synuclein is a cent rosome protein that may be involved in signal transduction pathways. Cell M otil. Cytoskeleton 49:218-228, 2001. (C) 2001 Wiley-Liss, Inc.