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Description

Golgi reassembly-stacking protein 1 (UniProt: O35254, also known as Golgi peripheral membrane protein p65, Golgi reassembly-stacking protein of 65 kDa, GRASP65) is encoded by the Gorasp1 (also known as Grasp65) gene in rat. GRASP65 is a Golgi structural protein and mediates cisternae stacking via self-aggregation as well as interactions with other Golgi membrane-docking proteins, such as GM130. Golgi fragmentation results from amyloid beta accumulation, which causes activation of Cdk5 and phosphorylation of GRASP65 resulting in Golgi fragmentation. At least eight GRASP65 phosphorylation sites have been identified. GRASP65 phosphorylation during mitosis and dephosphorylation after mitosis are required for Golgi disassembly and reassembly during the cell cycle. Golgi fragmentation in Alzheimer s disease brains accelerates amyloid precursor protein (APP) trafficking and further enhances amyloid peptide (Ab) production. Expression of non-phosphorylatable mutants of GRASP65 or the inhibition of Cdk5 is shown to rescue the Golgi structure and reduce Ab40 and Ab42 production. GRASP65 mutants are also reported to reduce Ab secretion by increasing alpha cleavage of the APP. (Ref.: Joshi G., et al. (2013). Proc. Natl. Acad. Sci. USA 111(13): E1230-E1239).