Association of dystrophin-related protein 2 (DRP2) with postsynaptic densities in rat brain.

The fundamental function of the membrane-associated cytoskeletal proteins dystrophin and utrophin remains unclear. To gain further insights into the dystrophin family of proteins, we have studied dystrophin-related protein 2 (DRP2), whose expression is largely confined to the vertebrate central nervous system. Both human and rat DRP2 are expressed from two alternative but neighboring transcriptional start sites and have simple transcript structures. Antibodies raised against DRP2 detect a characteristic quartet of bands ( approximately 100-120 kDa) in Western blots of rat brain. The DRP2 protein is associated with brain membrane fractions and highly enriched in the postsynaptic density. Immunohistochemistry shows DRP2 to be widely distributed in a punctate pattern on neuronal dendrites and in neuropil, with particular concentration in regions of the brain involved in cholinergic synaptic transmission. Given the presence of utrophin in the cholinergic neuromuscular junction, and perturbations of cholinergic transmission in dystrophin-deficient nematodes, our findings may suggest a role for DRP2 in the organization of central cholinergic synapses. Copyright 2000 Academic Press.