LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors

doi:10.1016/S0968-0004(00)01583-8

Trends in Biochemical Sciences

Volume 25, Issue 6, 1 June 2000, Pages 284-289

https://doi.org/10.1016/S0968-0004(00)01583-8 Get rights and content

Abstract

A number of unusual seven-transmembrane molecules have recently been characterized that have significant amino acid sequence similarity within the membrane-spanning hydrophobic regions and intervening loops to members of G-protein-coupled receptor family B. However, in contrast to the family-B G-protein-coupled receptors, these molecules have unusually large N-terminal extracellular domains that contain a number of well- characterized protein modules. The range of cell types expressing these complex molecules and their potential roles in cell adhesion and signalling have become a major focus of research in a number of biological systems.

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Sequence characteristics

In addition to the significant sequence similarity within the TM7 region, which ranges from approximately 25 to 70% identity, most of the individual members of the LNB-TM7 group share two further homologous extracellular regions: first, a stalk region containing approximately 20% Ser and Thr residues, which is probably modified by extensive O-glycosylation and therefore resembles a mucin domain and second, a characteristic motif (Cys-box) situated immediately N-terminal to TM1. This conserved

The EGF-TM7 proteins

The EGF-TM7 molecules were initially believed to be restricted to populations of leukocytes (Table 1). However, although F4/80 is indeed restricted to cells of the macrophage lineage, it appears that EMR1 and CD97 are also expressed by non-immune cell types. These molecules contain a variable number of N-terminal extracellular EGF domains that are encoded by individual exons and capable of generating multiple receptor isoforms through alternative RNA splicing¹¹.

F4/80 and EMR1

The F4/80 antibody specifically

Adhesion or signalling, or both?

Based on the extracellular domains of the various LNB-TM7 members, it could be envisaged that these molecules participate in cell adhesion, either by binding to components of the extracellular matrix or in cell–cell interactions. Indeed, CD97 has been shown to bind to CD55 (decay accelerating factor), a glycosyl-phosphatidylinositol (GPI)-linked cell-surface molecule that plays a role in regulating complement activation²⁷. Interestingly, the smallest isoform of CD97, which is generated through

Clues to physiological function

As stated previously, the complexity of the various LNB-TM7 molecules suggests possible dual roles as adhesion and signalling molecules. Indeed, intracellular signal transduction via the TM7 component might result from ligand binding to specific domains within the extracellular region. At present, the physiological processes in which these cell-surface molecules play a role are largely unknown. However, certain members of the LNB-TM7 group deserve further discussion in terms of possible

Concluding remarks

The LNB-TM7 group of cell-surface molecules described in this article defines a novel subset of family-B GPCRs (see also Box 1). The deduced protein sequences of LNB-TM7s show similarity to the previously described family-B GPCRs within the TM7 region and intervening loops, however, they are unusual insofar as they comprise large and complex extracellular regions composed of various protein domains (Fig. 1). Although the physiological functions of the LNB-TM7s are largely unknown, the

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Acknowledgements

Martin Stacey is funded through a BBSRC/Roche CASE studentship and Hsi-Hsien Lin is supported by the Welcome Trust Initiative for Cardiovascular Research. We are grateful to the Medical Research Council, UK, for their continued support.