Structural analysis of human CEACAM1 oligomerization

IntroductionThe glycoprotein Carcinoembryonic Antigen‐related Cell Adhesion Molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. It is expressed in a variety of tissues including epithelial, immune, as well as endothelial cells, and is crucial to diverse physiological and pathological mechanisms. This review aims to provide a comprehensive understanding of CEACAM1's multifaceted roles in vascular biology and inflammatory processes.MethodsDirected literature research was conducted using databases, such as PubMed, and relevant studies were categorized based on the physiological effects of CEACAM1.ResultsCEACAM1 plays a pivotal role in vascular homeostasis, particularly influencing the formation, maturation, and aging of blood vessels, as well as the endothelial barrier function. It supports endothelium‐dependent vasodilation and nitric oxide formation, thus promoting vascular integrity and regulating blood pressure. Additionally, CEACAM1 is of emerging importance to vascular inflammation and its potential clinical consequences.ConclusionCEACAM1 is a crucial regulator of vascular homeostasis and inflammation with significant implications for cardiovascular health. Despite the lack of understanding of tissue‐specific modulation and isoform‐dependent mechanisms, CEACAM1 could be a promising therapeutic target for the prevention of cardiovascular disease in the future.

CEACAM1 in vascular homeostasis and inflammation

Götz,

Rueckschloss,

Ergün

et al. 2024

The role of CEACAMs in neutrophil function

Skubitz

2024

BackgroundIn addition to the long‐known antibacterial actions of neutrophils, neutrophils are recognized to have a variety of other effects and are functionally diverse. Neutrophils can either stimulate or inhibit B cells and T cells, regulate NK development and activity, augment or direct the resolution of inflammation, act as myeloid‐derived suppressor cells, modulate tumour growth and metastasis and trigger autoimmune diseases. CEACAMs 1, 3, 6 and 8 are expressed on human neutrophils.MethodsA literature review was performed on the role of CEACAMs in neutrophil function.ResultsCEACAMs 1, 6 and 8 can be upregulated from intracellular stores, while CEACAM3, an opsonin‐independent phagocytic receptor, is constitutively expressed. CEACAM1 has an intracellular ITIM motif and an ITSM motif, and CEACAM3 has an ITAM‐like motif; CEACAMs 6 and 8 are glycosylphosphatidylinositol‐linked. CEACAM8 can also be released in a soluble form. These CEACAMs can interact with multiple other host CEACAMs as well as other molecules on bacteria, fungi and host cells, both transmitting and receiving signals. Known CEACAM‐binding pathogens bind the CFG face of the N domain which is also important in CEACAM‐CEACAM binding, although the ABDE face also appears to be involved in higher‐order oligomers.ConclusionsUnderstanding the exact role of each individual CEACAM in human neutrophils is complicated by the fact that the neutrophil CEACAMs can interact with multiple ligands. The data demonstrates some of the many roles of CEACAMs in neutrophil function and the extensive role of the neutrophil in human biology beyond its classical role as a short‐lived phagocyte.

Structural aspects of CEACAM1 interactions

Gandhi,

Huang,

Sun

et al. 2024

Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) is a membrane protein that plays an important role in a variety of immune and non‐immune functions. Such functions are regulated by its activity as a homophilic ligand but also through its ability to interact as a heterophilic ligand with various host proteins. These include CEACAM5, T cell immunoglobulin‐mucin like protein‐3 (TIM‐3) and, potentially, protein death protein 1 (PD‐1). Furthermore, CEACAM1 is targeted by various pathogens to allow them to invade a host and bypass an effective immune response. Clinically, CEACAM1 plays an important role in infectious diseases, autoimmunity and cancer. In this review, we describe the structural basis for CEACAM1 interactions as a homophilic and heterophilic ligand. We discuss the regulation of its monomeric, dimeric and oligomeric states in cis and trans binding as well as the consequences for eliciting downstream signalling activities. Furthermore, we explore the potential role of avidity in determining CEACAM1's activities.