α-synuclein increases the cellular level of phospholipase Cβ1

alpha-Synuclein is a conserved protein that is a key component in neurodegenerative plaques [1,2]. alpha-Synuclein binds strongly to phospholipase C beta (PLC beta) and promotes Ca2+ release in cells. Here, we show that expression of a-synuclein increases the cellular level of PLC beta 1 in two neuronal cell lines: PC12 and SK-N-S-SH. The increase in PLC beta 1 is not accompanied by changes in the level of RNA or in ubiquitination. Instead, we find that alpha-synuclein protects PLC beta 1 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 G alpha(q). We find that in SK-N-SH cells, alpha-synuclein reduced degradation of PLC beta 1 by calpain during Ca2+ signaling allowing the enzyme to remain sensitive to G alpha(q) activation. Taken together, our studies show that alpha-synuclein protects the integrity of PLC beta 1 and its ability to be activated by G alpha(q), which may in turn impact Ca2+ signaling. 2012 Elsevier Inc. All rights reserved.