C1q: structure, function, and receptors

C1q is the first subcomponent of the C1 complex of the classical pathway of complement activation. Several functions have been assigned to C1q, which include antibody-dependent and independent immune functions, and are consid ered to be mediated by C1q receptors present on the effector cell surface. There remains some uncertainty about the identities of the receptors that m ediate C1q functions. Some of the previously described C1q receptor molecul es, such as gC1qR and cC1qR, now appear to have less of a role in Clq funct ions than in functions unrelated to C1q. The problem of identifying recepto r proteins with complementary binding sites for C1q has been compounded by the highly charged nature of the different domains in C1q. Although newer c andidate receptors like C1qR(P) and CR1I have emerged, full analysis of the C1q-C1q receptor interactions is still at an early stage. In view of the d iverse functions that C1q is considered to perform, it has been speculated that several C1q-binding proteins may act in concert, as a C1q receptor com plex, to bring about C1q mediated functions. Some major advances have been made in last few years. Experiments with gene targeted homozygous C1q-defic ient mice have suggested a role for C1q in modulation of the humoral immune response, and also in protection against development of autoimmunity. The recently described crystal structure of Acrp-30, which is a serum protein s ecreted from adipocytes, has revealed a new C1q/TNF superfamily of proteins . Although the members of this superfamily may have diverse functions, ther e may be a common theme in their phylogeny and modular organisation of thei r distinctive globular domains. (C) 2000 Elsevier Science B.V. All rights r eserved.