Signal Reception

Cell signaling definition

Cell signaling is the process by which a cell reacts to signals–typically chemical in nature–from its external environment through protein receptors. Cell signaling can take place between cells (intercellular signaling) and within the cell (intracellular signaling).

There are various types of cell signaling. Cells can release ligands that bind to receptors within the same cell. This process is called autocrine signaling. Cells can also communicate with nearby cells in a process called paracrine signaling. Cells in an organism can also receive signals via hormones from cells in distant parts of the body. This process is called endocrine signaling.

Three stages of cell signaling: reception, transduction, and response

Cell signaling has three basic stages:

1. Signal reception: The cell detects a signal when a signaling molecule called a ligand binds to a receptor protein on the cell surface.

2. Signal transduction: The ligand reconfigures the receptor protein. The signal is relayed by each molecule changing the next molecule in the pathway.

3. Cellular response: The signal initiates a specific cellular process.

This article will focus on the first step of cell signaling, signal reception.

Definition of signal reception, ligands, and receptors in biology

Signal reception occurs when a ligand binds to a receptor protein in or on the surface of the plasma membrane. A ligand is a molecule that delivers signals, while a receptor is a molecule to which a ligand binds. Upon binding of the ligand, receptors initiate a physiological response.

Both ligands and receptors have a high level of specificity: typically, a ligand binds to a specific receptor. For example, growth factor receptors bind growth factors (and different subtypes of receptors can bind different types of growth factors), and dopamine receptors bind dopamine. In addition to chemical signals, some receptors can also detect light, heat, pressure, and other external stimuli.

Types of ligands

Ligands come in varying forms and sizes. Here we will discuss hydrophobic ligands and water-soluble ligands.

Small hydrophobic ligands

Small hydrophobic ligands such as steroid hormones directly diffuse through the interior of the plasma membrane and interact with internal or cytoplasmic receptors. Some steroid hormones can also bind to receptors located on the cellular surface.

Steroids are lipids with four fused rings on their hydrocarbon skeleton, which are connected to various functional groups depending on the kind of steroid. Testosterone (the male sex hormone), estradiol (the female sex hormone), and cholesterol (a crucial structural element of biological membranes and a precursor to steroid hormones) are all examples of steroid hormones.

Water-soluble ligands

Water-soluble ligands are polar so they cannot pass through the plasma membrane on their own. There are also water-soluble ligands that are too large to enter the membrane at all. As such, most water-soluble ligands bind to cell-surface receptors on the plasma membrane where extracellular signals are turned into intracellular signals. This group of ligands includes peptides and proteins.

Types of cell receptors

There are two types of cell receptors: internal and cell-surface receptors. We will also go into the three main categories of cell-surface receptors.

Internal receptors

Cell surface receptors

Cell surface receptors span the plasma membrane, meaning each receptor has extracellular (outside the cell), transmembrane (in the interior of the cell membrane), and cytoplasmic or intracellular (in the cytoplasm) domains.

Unlike internal receptors, cell-surface receptors need to convert extracellular signals into intracellular signals in a process called signal transduction. Ligands that bind with cell-surface receptors are not required to enter the cell.

Ion channel receptors

Ion channel-linked protein receptors work by binding a ligand and then opening a channel across the plasma membrane that allows specific ions to pass through (Fig. 1).

This type of cell surface receptor has a wide membrane-spanning region in which a channel can be constructed. Many amino acids in the transmembrane region are hydrophobic, so they are able to interact with the phospholipid fatty acid tails which constitute the core of the plasma membrane.

On the other hand, amino acids lining the inside of the ion channel are hydrophilic, so they can allow water or ions to pass through. When a ligand attaches to the extracellular region of the channel, the proteins undergo shape change to accommodate the entry of ions like sodium, calcium, and hydrogen.

Enzyme-linked receptors

Enzyme-linked receptors are found on the surface of the cell membrane. Some have an intracellular domain that interacts with enzymes, while others have an intracellular domain that is, in itself, an enzyme. Most enzyme-linked receptors have large extracellular and intracellular domains, with the region spanning the membrane consisting of a single alpha-helical region of a peptide strand.

When a ligand binds to the extracellular region, a signal is sent through the membrane, which activates the enzyme. The activated enzyme triggers a series of reactions that leads to a cellular response.

Enzyme-linked receptors allow signaling molecules to influence cell function without actually entering the cell since they interact with both extracellular signals and molecules present inside the cell. This is crucial as the majority of signaling molecules are either charged or too large to pass through the plasma membrane.

G Protein coupled receptors

G protein coupled receptors work by binding a ligand and then activating a type of membrane protein known as a G protein, which then interacts with an ion channel or an enzyme in the plasma membrane. G proteins are made up of several subunits:

• The alpha subunit (Gα) binds and hydrolyzes Guanosine triphosphate (GTP)

• The beta and gamma subunits (Gβγ) inhibit Gα and take part in signaling reactions

G protein coupled receptors span the membrane 7 times and contain a guanine nucleotide exchange (GEF) domain.

As such, when G protein coupled receptors bind ligands, the GEF domain catalyzes Gα to bind GTP. Gα-GTP dissociates from the Gβγ, and then some Gα subunits stimulate the activities of subsequent enzymes in the series, while others inhibit them (Fig. 2).

Example of signal reception in biology

An example of an enzyme-linked receptor is the tyrosine kinase receptor (Fig. 3). A protein kinase adds phosphate groups from ATP to a protein molecule. The tyrosine kinase receptor transfers phosphate groups specifically to tyrosine residues.

When the signal molecules bind to the extracellular region of two adjacent tyrosine kinase receptors, the two receptors undergo dimerization. Then, the tyrosine residues on the intracellular domain of the receptors undergo phosphorylation, enabling them to transmit the signal to the next messenger within the cytoplasm.