TARGETING OF SCG10 TO THE AREA OF THE GOLGI-COMPLEX IS MEDIATED BY ITS NH2-TERMINAL REGION

SCG10 is a neuronal growth-associated protein that is concentrated in the growth cones of developing neurons. SCG10 shows a high degree of s equence homology to the ubiquitous phosphoprotein stathmin, which has been recently identified as a factor that destabilizes microtubules by increasing their catastrophe rate, Whereas stathmin is a soluble cyto solic protein, SCG10 is membrane-associated, indicating that the prote in acts in a distinct subcellular compartment, Identifying the precise intracellular distribution of SCG10 as well as the mechanisms respons ible for its specific targeting will contribute to elucidating its fun ction, The main structural feature distinguishing the two proteins is that SCG10 contains an NH2-terminal extension of 34 amino acids, In th is study, we have examined the intracellular distribution of SCG10 in PC12 cells and in transfected COS-7 cells and the role of the NH2-term inal domain in membrane-binding and intracellular targeting, SCG10 was found to be localized to the Golgi complex region, We show that the N H2-terminal region (residues 1-34) was necessary for membrane targetin g and Golgi localization. Fusion proteins consisting of the NH2-termin al 34 amino acids of SCG10 and the related protein stathmin or the unr elated protein, beta-galactosidase, accumulated in the Gels, demonstra ting that this sequence was sufficient for Golgi localization, Biosynt hetic labeling of transfected COS-7 cells with [H-3]palmitic acid reve aled that two cysteine residues contained within the NH2-terminal doma in were sites of palmitoylation.