CAST2: identification and characterization of a protein structurally related to the presynaptic cytomatrix protein CAST.
The cytomatrix at the active zone (CAZ) is thought to define the site of Ca2+-dependent exocytosis of neurotransmitters. We have recently identified a novel CAZ protein from rat brain which we have named CAST (CAZ-associated structural protein). CAST forms a large molecular complex with other CAZ proteins such as Bassoon, RIM1 and Munc13-1, at least through direct binding to RIM1. Here, we have identified a rat protein that is structurally related to CAST and named it CAST2. Subcellular fractionation analysis of rat brain shows that CAST2 is also tightly associated with the postsynaptic density fraction. Like CAST, CAST2 directly binds RIM1 and forms a hetero-oligomer with CAST. In primary cultured rat hippocampal neurones, CAST2 co-localizes with Bassoon at synapses. Furthermore, immunoelectron microscopy reveals that CAST2 localizes to the vicinity of the presynaptic membrane of synapses in mouse brain. Sequence analysis reveals that CAST2 is a rat orthologue of the human protein ELKS. ELKS has also recently been identified as Rab6IP2 and ERC1. Accordingly, the original CAST is tentatively re-named CAST1. These results indicate that CAST2 is a new component of the CAZ and, together with CAST1, may be involved in the formation of the CAZ structure.
Deguchi-Tawarada
Maki
M
KAN Research Institute, Kyoto Research Park, Shimogyo-ku, Kyoto 600-8815, Japan.
Inoue
Eiji
E
Takao-Rikitsu
Etsuko
E
Inoue
Marie
M
Ohtsuka
Toshihisa
T
Takai
Yoshimi
Y
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D013569:Synapses / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C479909:ERC1 protein, rat; C479908:ERC2 protein, rat; D009419:Nerve Tissue Proteins; C491492:RIMS1 protein, human; C107293:Rim protein, mammalian; C491490:Rims1 protein, mouse; C491489:Rims1 protein, rat; D019204:GTP-Binding Proteins