title: α-Synuclein increases the cellular level of phospholipase Cβ1.
abstract: 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 Gα(q). 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 Gα(q) activation. Taken together, our studies show that α-synuclein protects the integrity of PLCβ1 and its ability to be activated by Gα(q), which may in turn impact Ca2+ signaling.
authors.affiliation: Department of Physiology & Biophysics, Stony Book University, Stony Brook, NY 11794-8661, USA.
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Guo
authors.forename: Barbara
authors.initials: B
authors.lastname: Rosati
authors.forename: Suzanne
authors.initials: S
authors.lastname: Scarlata
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D020536:Enzyme Activators / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry; D054799:Phospholipase C beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D051381:Rats; D014158:Transcription, Genetic; D014357:Trypsin / Q000737:chemistry; D054875:Ubiquitination; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D020536:Enzyme Activators; D010446:Peptide Fragments; D051844:alpha-Synuclein; D000001:Calcimycin; C518033:PLCB1 protein, human; D054799:Phospholipase C beta; D014357:Trypsin; D002154:Calpain