Functional Implication Of GRIP1 And GRIP2 To Neuronal Injury In The Rat Brain After Local Cerebral Ischemia

The basic communication between neurons is synape,and it was divided inio excitatiory and inhibitory synapse.In excitatory synapes ,a signal-transmitting neuron secretes glutamate (Glu) -a chemical messenger that diffuses across the synaptic cleft to bind to glutamate receptors (GluR) concentrated in the postsynaptic membrane of the receiving neuron. GluR can be subdivided based on their pharmacology into three major classes: AMPA, kainate, and NMDA receptors et al.,. AMPA receptor in the postsynaptic membrane can bind with Glu,which can induce the depolarization.NMDA receptor and AMPA receptor are all ionotropic glutamate receptors. They concentrate at postsynaptic sites and largely colocalized in excitatory synapses. Both of them are heteromeric complexes composed of some homologous subunits that differentially combine to form a variety of AMPA or NMDA receptor subtypes and play different roles. NMDA receptor are relatively fixed, AMPA receptors cyclesynaptic membraneson and off. AMPA receptors mediate rapid excitatory synaptic transmission whereas NMDA receptors initiate synaptic plasticity. .Mechanisms for controlling synaptic expression of these two receptors classes are different. Synaptic localization and clustering of ion channels and neurotransmitter receptors are necessary for normal synaptic transmission . There is a large family of interacting proteins regulate AMAP receptors turnover at synapses , they can form a complex to regulate the distribution and function of the receptors, and have effects on the neuroal transmission.Ionotropic glutamate receptors of the AMPA largely colocalize with NMDA receptors in excitatory synapses at postsynaptic site, but they do not interact with PSD-95 family proteins. Instead, the AMPA receptor subunits GluR2/3 bind specifically to other PDZ proteins, termed glutamate receptor-interacting protein (GRIP), AMPA receptor-binding protein (ABP), and protein interacting with C kinase 1 (PICK1). Both GRIP1 and GRIP2 contain seven PDZ domains and no other recognizable motif, ABP resembles GRIP in primary sequence; it differs from GRIP most notably in lacking the C-terminal seventh PDZ domain. The C-terminal sequence (-ESVKI) shared by AMPA receptor GluR2/3 subunits is reported to bind selectively to the forth and fifth PDZ domains (PDZ4/5) of GRIP and the third, fifth, and sixth PDZ domains of ABP. The GRIP1 and GRIP2 antibodies specifically detected GRIP1 and GRIP2 as 135 and 130 kDa proteins, respectively. The GRIP1 protein was expressed in brain and testis but was not detected in heart, spleen, lung, liver, skeletal muscle, kidney, and intestine, whereas the major forms of GRIP2 were selectively expressed in brain (Fig. 2a). GRIP1 and GRIP2 had similar distributions in rat brain regions and were enriched in the olfactory bulb, cortex, and hippocampus and were colocalized in many regions. GRIP1 expression in rat brain was detected in earlyembryonic stages, peaked at approximately postnatal day 6-8, in contrast, GRIP2 expression was relatively low early in development and increased postnatally, reaching a peak at postnatal day 14, similar to what is observed for GluR2. we could also find enrichment of GRIP in GABAergic neurons and in GABAergic nerve terminals. GRIPl and GRIP2 are AMPA receptor binding proteins potentially involved in the targeting of AMPA receptors to synapses. GRIPl also may play functional roles at both excitatory and inhibitory synapses, as well as in early neuronal development.GluR can regulate the excitatory synaptic transmission in the CNS, they play roles in neuronal development, excitotoxicity, and synaptic plasticity. During acute injury of neural anoxia or ischemia, Glutamate are necessary .In normal condition, the density of extracellular EAA(excitatory amino acids) is mediated by the ingestion of neurons and glia cells , and can not run up to hurt the neurons. When anoxia or ischemia occur , the density of extracellular EAA increase dramatically because of the increasing of releasing ,the decreasing of ingestion and the overflowing of in...