Functional analysis for signal transducsion via GPI-anchord neural cell adhesion molecules of contactin subgroup

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Contactin subgroup molecules including contactin, TAG-1, NB-2, NB-3, BIG-1 and BIG-2 are GPI-anchored neural adhesion molecules belonged in immunoglobulin-superfamily(IGSF). A GPI-anchored molecule is known to attribute to detergent insoluble low-density fractions (lipid rafts) in which many signal transducing molecules are co-localized. In this study, I have investigated the functions of these molecules on the formation of brain organization and higher brain functions, especially focusing on signal transduction via synaptic transmission. Results were as follows.1)Contactin and NB-3 as well as contactin associated protein (Caspr 1) which is cis-interacted with contactin on the same side of plasma membrane were distributed in lipid raft fraction derived from synaptosome (postsynaptic density, PSD) of rat cerebral cortex.2)PSD-95 that is one of folding protein specifically localized in PSD was immunoprecipitated with both contactin and NB-3. And Caspr1 was detected in the precipitants with contactin, but not in that with NB-3.3)Total amount of proteins co-localized in the PSD derived from 30 month-old rat cortical synaptosome was less than that in PSD from 6 month-old. In contrast, cholesterol was much more contained in old PSD compared from young adult PSD. I have currently analyzed what kind of proteins were fluctuated by aging in cortical PSD fraction.4)Caspr2 and 4 belonging to the Caspr family were also localized in lipid raft. Analysis by East two-hybrid system, some interesting proteins were found to interact with the intracellular portion of either Caspr2 and 4. I have currently characterizing those proteins.These results suggested that contactin and NB-3 may cis-interact with caspr family and possibly involve in the postsynaptic functions.