21.3: Types of Receptors: Cell Surface Receptors

Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma membrane and performs signal transduction, converting an extracellular signal into an intracellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types.

Each cell-surface receptor has three main components: an external ligand-binding domain called the extracellular domain, a hydrophobic membrane-spanning region called a transmembrane domain, and an intracellular domain inside the cell. The size and extent of each of these domains vary widely, depending on the type of receptor. Cell-surface receptors are involved in most of the signaling in multicellular organisms. There are three general categories of cell-surface receptors: ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors.

Because cell-surface receptor proteins are fundamental to normal cell functioning, it should be no surprise that a malfunction in any of these proteins could have severe consequences. Errors in the protein structures of certain receptor molecules have been shown to play a role in hypertension (high blood pressure), asthma, heart disease, and cancer.

This text is adapted from Openstax, Biology 2e, Chapter 9 Cell communication, Section 9.1: Signaling molecules and cellular receptors.

Transmembrane receptors are proteins on the cell surface that function as signal transducers and initiate intracellular signaling cascades.

They may be classified as ion channel receptors, G-protein coupled receptors, and enzyme-linked receptors.

Ion channel receptors are divided into two subtypes. The ligand-gated channels open when a ligand binds to the receptor allowing ions to diffuse through the channel.

In contrast, the voltage-gated channels open and close in response to changes in the charge difference across the membrane, allowing ions to move into or out of the cell.  

G-protein coupled receptors or GPCRs have their cytoplasmic domain coupled to a heterotrimeric GTP-binding protein. Ligand binding stimulates the exchange of the GDP in the alpha subunit of G-protein with a GTP. This causes the alpha and beta-gamma subunits to dissociate and interact with other effector proteins.

Enzyme-linked receptors either have a cytoplasmic domain that can function as an enzyme or associate directly with intracellular enzymes. Ligand binding promotes receptor dimerization and enzyme activation.