Antibodies

Monocyte chemotractant protein-1 (MCP-1), also known as CCL2, is a key chemokine involved in the migration of monocytes and macrophages to sites of active inflammation. It is a member of the C-C/beta family of cytokines, characterized by the Cys-Cys sequence at its N-terminus (1). MCP-1 is tethered to endothelial cells via glycosaminoglycans within the plasma membrane (2). MCP-1 cleavage by MMP-12 is necessary for MCP-1 to interact with its receptor CCR2.

Antibodies play an important role in the innate immune system by circulating in the bloodstream to fight off invading pathogens. IgG is the most prevalent of the five classes of antibodies (IgA, IgD, IgE, IgG, and IgM) and is the only one transmitted from a mother to her offspring. IgG is transported across the epithelium of the placenta by the neonatal Fc receptor (FcRn) (1). FcRn is a 40 kDa protein encoded by the FCGRT gene. FcRn binds to the Fc domain of IgG and transports the antibody in a pH dependent mechanism.

While known for their role in programmed cell death, caspases are also essential for mediating inflammatory responses and innate immunity. Binding of microbial molecules by pattern recognition receptors triggers the formation of the multiprotein inflammasome complex and the activation of caspase-1 (1). Caspase-1 is then able to mediate the activation and secretion of proinflammatory cytokines including interleukin-1. In addition to caspase-1, caspase-11 also plays an important role during the inflammatory response.

alpha-Synuclein is a 14 kDa protein encoded by the SNCA gene that is abundantly expressed in neurons. Within the neuron, alpha-Synuclein is densely localized on presynaptic terminals, indicating a potential role in synaptic transmission. Nitration at specific tyrosine residues promotes misfolding and aggregation of alpha-Synuclein. These aggregates are a major component of Lewy bodies, characteristic lesions of neurodegenerative disorders known as synucleinopathies.

Caspases are endoproteases that play important roles in the regulation of cell death and apoptosis. Caspase active sites contain a catalytic cysteine residue essential for the proteolytic cleavage of their substrates at conserved aspartic acid residues (1). Caspases are produced as inactive procaspase monomers in order to regulate their activity. Upon dimerization procaspases are cleaved to produce their active form (1). Caspases are typically grouped by their role in either cell death or inflammation.

Calreticulin is a calcium-dependent ER chaperone, involved in protein folding, maturation, and cellular localization. Calreticulin is a highly conserved 48 kDa protein encoded by the CALR gene. Calreticulin and its homolog calnexin regulate the folding and degradation of newly synthesized glycoproteins as they are translocated into the ER (1). Misfolded proteins recognized by calreticulin are targeted to the ER-associated degradation (ERAD) pathway. Within the ER, calreticulin also plays an important role in calcium homeostasis.

The 78 kDa glucose-regulated protein (GRP78) is the eukaryotic orthologue to the prokaryotic heat shock 70 kDa protein 5 (HSPA5). GRP78 is also sometimes referred to as BiP. GRP78 is a member of the HSP70 family and plays dynamic roles in protein regulation within the endoplasmic reticulum. GRP78 is the most abundant chaperone in the ER and plays an important role in regulating the unfolded protein response (UPR) (1). GRP78 forms a multiprotein chaperone complex with DNAJB11, HSP90B1, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1, and ERP29.

The mammalian forkhead O class transcription factors (FOXO) regulate diverse cellular processes such as metabolism, cell cycle, and apoptosis. Activity of these transcription factors can be regulated by diverse post-translational modifications including phosphorylation, acetylation, and ubiquitination (1). These modifications can alter nuclear transport, DNA binding, and protein-protein interactions to alter transcriptional activity. The best studied member of the FOXO family is FOXO1.

Caspase-2 is a highly conserved member of the caspase family involved in the initiation and execution of apoptosis. While its function is still poorly understood, caspase-2 is thought to be important for apoptosis in response to DNA damage, bacterial infection, or abnormal mitosis (1). Caspase-2 contains an N-terminal caspase recruitment domain, the large p19 subunit containing the active site, and the small C-terminal p12 subunit (1). In response to various apoptotic signals caspase-2 undergoes dimerization.

The structure and organization of the plasma membrane is maintained by an underlying network of cytoskeletal proteins including actin and spectrin. Adducin, a member of this protein network, binds to bundles and caps actin filaments and links them to spectrin. Adducin’s role in organizing the cytoskeletal meshwork at the plasma membrane is important in signal transduction, cell-cell adhesion, and cell migration (1).