Roles of neuregulin in synaptogenesis between mossy fibers and cerebellar granule cells

Neuregulins (NRGs), a large group of structurally related signaling protein s, are likely to have important roles in the development, maintenance and r epair of the nervous system and other selected tissues. We have demonstrate d, by using the major form of NRG cloned from the mouse cerebellum that bot h the soluble form and the membrane anchored form of NRG may serve differen t functions in synaptogenesis, The soluble form of NRG was produced by prot eolytic cleavage of the membrane anchored form of NRG, The proteolytic clea vage was promoted by protein kinase activation. The cleaved form of NRG tra nssynaptically regulated the expression of the NMDA (N-methyl-D-aspartate) receptor subunit NR2C as neurally-derived factors, whereas the membrane anc hored form of NRG showed a hemophilic binding activity between NRG beta 1s, In adult mice the membrane anchored form of NRG was concentrated in neuro- terminals of both granule cells and pontocerebellar mossy fibers. The fact that NRG can be functionally viewed as cell recognition molecules as well a s neurotrophic agents suggests new possibilities for the important class of molecules. J, Neurosci, Res. 59: 612-623, 2000, (C) 2000 Wiley-Liss, Inc.