α-Synuclein increases the cellular level of phospholipase Cβ1.

α-Synuclein is a conserved protein that is a key component in neurodegenerative plaques [1,2]. α-Synuclein binds strongly to phospholipase Cβ (PLCβ) and promotes Ca2+ release in cells. Here, we show that expression of α-synuclein increases the cellular level of PLCβ1 in two neuronal cell lines: PC12 and SK–N–S–SH. The increase in PLCβ1 is not accompanied by changes in the level of RNA or in ubiquitination. Instead, we find that α-synuclein protects PLCβ1 from trypsin digestion and from degradation by the Ca+2 activated protease calpain. Calpain removes the C-terminal region of the enzyme which mediates activation by Gαq. We find that in SK–N–SH cells, α-synuclein reduced degradation of PLCβ1 by calpain during Ca2+ signaling allowing the enzyme to remain sensitive to Gαq activation. Taken together, our studies show that α-synuclein protects the integrity of PLCβ1 and its ability to be activated by Gαq, which may in turn impact Ca2+ signaling.