(1) Book 3: Cell Signalling

Cell Signalling

Cell signalling is the process by which cells communicate with one another - a hallmark of

multicellular organisms.

• It ensures that cellular activities such as growth, differentiation, metabolism and cell division

occur in the right cells, at the right time, and in proper coordination with the other cells.

• Hence the organism grows, develops and functions as an integrated and coherent whole,

consisting of a multitude of cells in diverse tissues and organs, rather than a massive

collection of independently functioning cells.

• Cells communicate most often by detecting and sending a variety of chemical signals.

Signalling cells release many different kinds of chemical compounds referred to as signal

molecules that serve as chemical messengers. Signal molecules include proteins, small

peptides, amino acids, and other small molecules (nucleotides, steroids, retinoids, fatty acid

derivatives, and dissolved gases such as nitric oxide and carbon monoxide). These signal

molecules bind to receptor proteins on the surface or in in the interior of target cells, which

then respond to the signals.

• Signalling cells may or may not be directly adjacent to their target cells. Communication

between cells can occur by direct contact (Fig. 1) or by secreted molecules that diffuse

locally or travel to other tissues to trigger a response in target cells

Regardless of the nature of the signal, the target cell responds by means of a specific

receptor, which specifically binds the signal molecule which then initiates a response in

the target cell

• As shown above, an individual cell requires multiple signals to survive (cell 1) and

additional signals to divide or differentiate (see cells 2 and 3).

• If deprived of appropriate survival signals, the cell undergoes apoptosis, a form of

programmed cell death (cell 4).

• Note that some signal molecules (not shown) can be inhibitory in nature or even induce

apoptosis.

• Signalling cells are thus able to coordinate over short and long ranges, various target cells’

diverse physiological functions which in turn require the tight regulation of cellular events

including gene expression, cell proliferation and cell movement.

Stages of Cell Signalling

1. Signal reception

2. Signal transduction

3. Cellular response

Stages of Cell Signalling — 1) Signal Reception

• Signal reception refers to the target cell’s detection of an extracellular signal molecule.

• A signal is detected when a signal molecule binds to a specific receptor protein located

at the cell’s surface or inside the target cell, examples include hormones and

neurotransmitters.

• Ligand-receptor interaction is highly specific. The signal molecule acts as a ligand

(generic term for any molecule that binds to specific sites on another molecule, often a larger

one), binding to a specific complementary site on the target cell’s receptor to form a

ligand-receptor complex.

• This causes the receptor protein to undergo a conformation change. For many receptors,

this change in conformation directly activates the receptor, enabling it to interact with

other molecules in the cell.

• There are two kinds of signal receptor proteins (Fig. 5):

o cell surface / extracellular / transmembrane receptors (located on the cell surface

membrane)

o intracellular receptors (located inside the cell) (not in 9477 H2 syllabus, FYI)

Stages of Cell Signalling — 2) Signal Transduction

Signal Transduction is the process by which a target cell converts an extracellular

signal into an intracellular signal that results in a specific cellular response.

• The formation of the activated ligand-receptor complex changes the conformation of

the receptor protein, initiating the process of transduction.

• Transduction sometimes occurs in a single step – as in the case for signalling mediated by

intracellular receptors (not in 9477 H2 Biology syllabus, FYI).

• More often, as in the case with cell surface receptors, transduction occurs via a multistep

signal transduction pathway consisting of a series of relay molecules.

• These relay molecules are usually proteins such as enzymes that operate in a specific

sequence.

o Each protein in the pathway typically acts by altering the conformation of and hence

activating or inhibiting the protein immediately downstream.

o As the conformational changes are usually brought about by phosphorylation, the

relay proteins in a signal transduction pathway are sequentially phosphorylated.

o This forms a phosphorylation cascade that transmits the signal received at the cell

surface into the cell.

• Transduction may also involve non-protein molecules that function as second messengers

o Second messengers through diffusion, rapidly relay the signal from the cell surface into

the cell interior.

Stages of Cell Signalling — 3) Cellular Response

A signal transduction pathway eventually leads to the regulation of one or more cellular

activities.

• The response may occur in the cytoplasm (cytoplasmic response) or may involve action in

the nucleus (nuclear response).

• Cytoplasmic response involves mainly changes in cell metabolism, including

o regulation of enzyme activity such as activation of cytoplasmic enzymes or other

proteins.

o cytoskeletal arrangement.

• Nuclear response involves changes in gene expression such as

o turning specific genes on or off in the nucleus, and hence synthesis of enzymes or

other proteins.