Chapter 39 – C1q Receptors

C1q, the recognition component of the classical complement pathway, also regulates numerous cellular processes independent of its role in complement activation. Among these processes is myeloid cell activation leading to enhanced engulfment of apoptotic cells and the regulation of proinflammatory cytokine production which is thought to be important in the prevention of autoimmunity. C1q deficiency results in a lupus-like autoimmune disease in humans, and there has been a significant effort to identify C1q receptors that might be effective targets for the manipulation of C1q-dependent cellular functions such as phagocytosis and cytokine regulation. C1q is a 460-kD hexamer containing a globular head region and collagen-like tail. Receptors for both the collagen like tail and globular head regions have been proposed and are described below. The described receptors are heterogeneous; two lack cytoplasmic tails and are found both intracellularly and extracellularly (gC1qR and calreticulin), two are Ig superfamily members (LAIR-1 and RAGE), one is a heterodimeric integrin (α2β1), two are scavenger receptors (SCARF1 and Megf10), one is a receptor for multiple complement components (CR1). In addition, two of the receptors have been previously described as receptors for collagen (α2β1 and LAIR-1), consistent with their ability to bind to the collagen-like tail of C1q. C1q is a soluble pattern-recognition receptor with a highly basic charge, it binds to multiple molecules and may regulate cell activation through multiple different receptors and/or receptor complexes. The putative C1q receptors are listed below in order of their identification.