Identification of syntaxin 1A as a novel binding protein for presenilin-1.
Mutations in the presenilin 1 gene have been shown to result in Alzheimer's disease. Presenilin 1 is a multi-transmembrane protein with a large hydrophilic loop near the C-terminus. This region is required for known functions of presenilin 1. We have constrained this loop within the active site of the bacterial protein, thioredoxin, to mimic its native conformational state. This hybrid protein was used as bait in a yeast two hybrid screen in an attempt to identify presenilin binding proteins. By this method syntaxin 1A, a synaptic plasma membrane protein, was identified as a novel binding protein for presenilin 1. In vitro experiments confirm the two-hybrid results suggesting that PS1 binds syntaxin under physiological conditions.
Smith
S K
SK
Molecular Neurobiology Unit, Department of Medicine (Care of the Elderly), University of Bristol, Bristol, BS2 8HW, UK.
Anderson
H A
HA
Yu
G
G
Robertson
A G
AG
Allen
S J
SJ
Tyler
S J
SJ
Naylor
R L
RL
Mason
G
G
Wilcock
G W
GW
Roche
P A
PA
Fraser
P E
PE
Dawbarn
D
D
D000544:Alzheimer Disease / Q000378:metabolism; D000954:Antigens, Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D015870:Gene Expression / Q000502:physiology; D005990:Glycerol; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011233:Precipitin Tests; D053764:Presenilin-1; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D013347:Subcellular Fractions / Q000737:chemistry; D013572:Synaptic Vesicles / Q000378:metabolism; D050827:Syntaxin 1; D013879:Thioredoxins / Q000737:chemistry / Q000235:genetics; D020798:Two-Hybrid System Techniques
D000954:Antigens, Surface; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; C494212:STX1A protein, human; D050827:Syntaxin 1; D013879:Thioredoxins; D005990:Glycerol