Cell surface and intracellular receptors play important roles in signal transduction. There are two main types of receptors - internal receptors located in the cytoplasm that directly influence gene expression, and cell surface receptors that span the plasma membrane and convert extracellular signals into intracellular signals. Cell surface receptors include enzyme-linked receptors with intracellular enzyme domains, ion channel-linked receptors that open channels for ion flow, and G-protein-linked receptors that activate intracellular G-proteins to transmit signals. Defects in cell surface receptors can cause diseases.

1. Cell surface and intracellular
receptors and their role in signal
mediation (general
information)

2. SIGNAL RECEPTORS
• The ability of a cell to respond to an extracellular signal depends on the
presence of specific proteins called receptors, which are located on the cell
surface or in the cytoplasm.
•
• Receptors bind chemical signals that ultimately trigger a mechanism to
modify the behaviour of the target cell.
• Cells may contain an array of specific receptors that allow them to respond
to a variety of chemical signals.
• Receptors are protein molecules in the target cell or on its surface that bind
to ligands.
• There are two types of receptors, internal receptors and cell-surface
receptors.

3. INTERNAL RECEPTORS
• Internal receptors, also known as intracellular or cytoplasmic
receptors, are found in the cytoplasm of target cells and respond
to hydrophobic ligand molecules that are able to travel across the
plasma membrane.
• Once inside the cell, many of these molecules bind to proteins
that act as regulators of mRNA synthesis (transcription) to
mediate gene expression.
• Gene expression is the cellular process of transforming the
information in a cell’s DNA into a sequence of amino acids, which
ultimately forms a protein.
• When the ligand binds to the internal receptor, a conformational
change is triggered that exposes a DNA-binding site on the
receptor protein.

4. • The ligand-receptor complex moves into the nucleus, then binds to specific regulatory
regions of the chromosomal DNA and promotes the initiation of transcription.
•
• Transcription is the process of copying the information in a cells DNA into a special
form of RNA called messenger RNA (mRNA); the cell uses information in the mRNA
(which moves out into the cytoplasm and associates with ribosomes) to link specific
amino acids in the correct order, producing a protein.
• Internal receptors can directly influence gene expression without having to pass the
signal on to other receptors or messengers.
• Hydrophobic signaling molecules typically diffuse across the plasma membrane and
interact with intracellular receptors in the cytoplasm. Many intracellular receptors are
transcription factors that interact with DNA in the nucleus and regulate gene
expression.

6. Cell-surface receptors
• Cell-surface receptors, also known as transmembrane receptors, are
integral proteins that bind to external signaling molecules.
• These receptors span the plasma membrane and perform signal
transduction, in which an extracellular signal is converted into an
intercellular signal.
• Because cell-surface receptor proteins are fundamental to normal cell
functioning, it should come as no surprise that a malfunction in any
one 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.

8. COMPONENTS AND TYPES
• Each cell-surface receptor has three main components: an external
ligand-binding domain, or extracellular domain; a hydrophobic
membrane-spanning region; and an intracellular domain.
• Cell-surface receptors are involved in most of the signaling in
multicellular organisms.
• There are three general categories of cell-surface receptors:
• enzyme-linked receptors,
• ion channel-linked receptors
• G-protein-linked receptors.

9. ENZYME LINKED RECEPTORS
• Enzyme-linked receptors are cell-surface receptors with intracellular domains that are
associated with an enzyme.
• In some cases, the intracellular domain of the receptor itself is an enzyme.
• Other enzyme-linked receptors have a small intracellular domain that interacts directly with
an enzyme.
• Enzyme-linked receptors normally have large extracellular and intracellular domains, but
the membrane-spanning region consists of a single alpha-helix in the peptide strand.
• When a ligand binds to the extracellular domain of an enzyme-linked receptor, a
signal is transferred through the membrane, activating the enzyme. Activation of the
enzyme sets off a chain of events within the cell that eventually leads to a
response.
•

10. Enzyme-linked receptor - tyrosine kinase receptor
• A kinase is an enzyme that transfers phosphate groups from ATP to
another protein.
• The tyrosine kinase receptor transfers phosphate groups to tyrosine
molecules.
• First, signaling molecules bind to the extracellular domain of two nearby
tyrosine kinase receptors.
• The two neighboring receptors then bond together, or dimerize.
• Phosphates are then added to tyrosine residues on the intracellular
domain of the receptors (phosphorylation).
• The phosphorylated residues can then transmit the signal to the next
messenger within the cytoplasm.

12. • Epidermal growth factor receptors are an example of receptor
tyrosine kinases that follows this mode of signaling.
• Defects in ErbB signaling in this family can lead to
neuromuscular diseases such as multiple sclerosis and
Alzheimer’s disease.

13. Ion channel-linked receptors
• Ion channel-linked receptors bind to a ligand and open a channel
through the membrane that allows specific ions to pass through.
• This type of cell-surface receptor has an extensive membrane-
spanning region with hydrophobic amino acids.
• Conversely, the amino acids that line the inside of the channel are
hydrophilic to allow for the passage of ions.
• When a ligand binds to the extracellular region of the channel, there is
a conformational change in the protein’s structure that allows ions
such as sodium, calcium, magnesium, or hydrogen to pass through

14. Ion channel-linked receptors open and allow ions to enter a cell. An example of an ion channel-linked receptor is found on
neurons. When neurotransmitters bind to these receptors, a conformational change allows sodium ions to flow across the cell
membrane, causing a change in the membrane potential.

15. G-protein-linked receptors
• G-protein-linked receptors bind to a ligand and activate an
associated G-protein.
• The activated G- protein then interacts with a nearby membrane
protein, which may be an ion channel or an enzyme.
• All G-protein-linked receptors have seven transmembrane domains,
but each receptor has a specific extracellular domain and G-protein-
binding site.
• Cell signaling using G-protein-linked receptors occurs as a cycle.
• Once the ligand binds to the receptor, the resultant shape change
activates the G-protein, which releases GDP and picks up GTP.

16. • The subunits of the G-protein then split into α and βγ subunits.
• One or both of these G-protein fragments may be able to
activate other proteins in the cell.
• After a while, the GTP on the active α subunit of the G-protein is
hydrolyzed to GDP and the βγ subunit is deactivated.
• The subunits re-associate to form the inactive G-protein and the
cycle begins again.
• G-protein linked receptors are used in many physiological
processes including those for vision transduction, taste, and
regulation of immune system and inflammation.

18. • http://utmadapt.openetext.utoronto.ca/chapter/9-2/
• https://rwu.pressbooks.pub/bio103/chapter/cell-communication/
• https://organismalbio.biosci.gatech.edu/chemical-and-electrical-
signals/intro-to-chemical-signaling-and-signal-transduction/