C1q: A fresh look upon an old molecule

Abstract

Originally discovered as part of C1, the initiation component of the classical complement pathway, it is now appreciated that C1q regulates a variety of cellular processes independent of complement activation. C1q is a complex glycoprotein assembled from 18 polypeptide chains, with a C-terminal globular head region that mediates recognition of diverse molecular structures, and an N-terminal collagen-like tail that mediates immune effector mechanisms. C1q mediates a variety of immunoregulatory functions considered important in the prevention of autoimmunity such as the enhancement of phagocytosis, regulation of cytokine production by antigen presenting cells, and subsequent alteration in T-lymphocyte maturation. Furthermore, recent advances indicate additional roles for C1q in diverse physiologic and pathologic processes including pregnancy, tissue repair, and cancer. Finally, C1q is emerging as a critical component of neuronal network refinement and homeostatic regulation within the central nervous system. This review summarizes the classical functions of C1q and reviews novel discoveries within the field.

Keywords: Autoimmunity; Complement C1q; Neurobiology; Pregnancy; Tumor; Wound healing.

Fig. 1

Schematic representation of the assembly of the C1q molecule and of the recombinant single chain globular region. C1q is assembled from three polypeptide chains (A, B and C) each containing an N-terminal collagen-like sequence and a C-terminal globular gC1q module. A particular inter-chain disulfide pattern results in a basic subunit comprised of two heterotrimeric collagen-like stalks prolonged by globular domains (C1q–GR). Three subunits associate to yield the full-length protein with a typical shape of a bouquet of six flowers. The crystal structure of the trimeric C1q–GR shows that the N- and C- terminal ends of the 3 chains are in close proximity which allowed insertion of short linkers between the gC1qA-gC1qC and gC1qC-gC1qB modules to yield a recombinant single chain construct.