Synaptotagmin 1 causes phosphatidyl inositol lipid-dependent actin remodeling in cultured non-neuronal and neuronal cells.
Here we demonstrate that a dramatic actin polymerizing activity caused by ectopic expression of the synaptic vesicle protein synaptotagmin 1 that results in extensive filopodia formation is due to the presence of a lysine rich sequence motif immediately at the cytoplasmic side of the transmembrane domain of the protein. This polybasic sequence interacts with anionic phospholipids in vitro, and, consequently, the actin remodeling caused by this sequence is interfered with by expression of a phosphatidyl inositol (4,5)-bisphosphate (PIP2)-targeted phosphatase, suggesting that it intervenes with the function of PIP2-binding actin control proteins. The activity drastically alters the behavior of a range of cultured cells including the neuroblastoma cell line SH-SY5Y and primary cortical mouse neurons, and, since the sequence is conserved also in synaptotagmin 2, it may reflect an important fine-tuning role for these two proteins during synaptic vesicle fusion and neurotransmitter release.
Department of Cell Biology, Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.
Anna-Karin
AK
Johnsson
Roger
R
Karlsson
D000199:Actins / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D051381:Rats; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism*; D050861:Synaptotagmin II / Q000378:metabolism; D000099182:Phosphoinositide 5-Phosphatases
D000199:Actins; D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases; D050863:Synaptotagmin I; D050861:Synaptotagmin II; D000099182:Phosphoinositide 5-Phosphatases; C494262:SYT2 protein, human; C494263:Syt2 protein, mouse