Botulinum neurotoxin E receptors and uses thereof
An isolated polypeptide comprising an amino acid sequence selected from amino acids 506-582 of SV2A, wherein position 573 is N and is glycosylated, or amino acids 449-525 of SV2B, wherein position 516 is N and is glycosylated. The present invention also provides an antibody that binds specifically to the polypeptide, an isolated nucleic acid comprising a polynucleotide that encodes the polypeptide; a method for reducing BoNT/E toxicity in an animal; a method for identifying an agent that blocks or inhibits binding between BoNT/E and an SV2A or SV2B protein; a method for monitoring synaptic vesicle endo- or exocytosis, a method for specifically delivering a chemical entity to a cell which has a specific receptor to a BoNT toxin. Also provided are a chimeric toxin for targeting a proteolytic domain of a toxin to a cell, the chimeric toxin comprising a catalytic or proteolytic domain of the BoNT toxin, and a ligand or a fragment thereof for a non-BoNT receptor on the cell; a method for targeting a proteolytic domain of a BoNT toxin to a cell, an isolated non-neuronal cell comprising a BoNT toxin receptor; and a method for screening for an inhibitor of a BoNT toxin.
1. A method for reducing botulinum neurotoxin E (BoNT/E) toxicity in an animal comprising administering to the animal a synaptic vesicle membrane protein 2A (SV2A) or synaptic vesicle membrane protein 2B (SV2B) polypeptide, wherein the SV2A polypeptide is at least 90% identical to SEQ ID NO:4, and has a glycosylated N residue at position 573, and wherein the SV2B polypeptide comprises the amino acid sequence set forth as SEQ ID NO:7 and has a glycosylated N at position 516.
2. The method of claim 1 , wherein the animal is a mammal.
3. The method of claim 2 , wherein the mammal is a human.
4. The method of claim 1 , wherein the SV2A polypeptide comprises an amino acid sequence that is at least 90% identical to residues 506-582 of the amino acid sequence set forth as SEQ ID NO:4.
5. The method of claim 1 , wherein the SV2A polypeptide comprises the sequence set forth as residues 506-582 of the amino acid sequence set forth as SEQ ID NO:4.
6. The method of claim 1 , wherein the polypeptide is a full length SV2A or SV2B polypeptide.