The presentation gives a brief introduction to the process of cell signalling.

1. Introduction to
Cell Signalling
BY:
Rakshita
Srivastava
17BCB0116
DIGITAL ASSIGNMENT
CELLBIOLOGY AND BIOCHEMISTRY

2. Overview
 Cells typically communicate using chemical signals.
 These chemical signals, which are proteins or other molecules produced by a
sending cell, are often secreted from the cell and released into the extracellular
space.
 There, they can float – like messages in a bottle – over to neighbouring cells.
 Not all cells can “hear” a particular chemical message.
 In order to detect a signal (that is, to be a target cell), a neighbor cell must have
the right receptor for that signal.

3. Overview
 When a signaling molecule binds to its receptor, it alters the shape or activity of
the receptor, triggering a change inside of the cell.
 Signaling molecules are often called ligands, a general term for molecules that
bind specifically to other molecules (such as receptors).
 The message carried by a ligand is often relayed through a chain of chemical
messengers inside the cell.
 Ultimately, it leads to a change in the cell, such as alteration in the activity of a
gene or even the induction of a whole process, such as cell division. Thus, the
original intercellular (between-cells) signal is converted into an intracellular
(within-cell) signal that triggers a response.

4. Introduction
 Cell signaling is part of a complex system of communication that governs basic
cellular activities and coordinates cell actions.
 The ability of cells to perceive and correctly respond to their microenvironment is
the basis of development, tissue repair, and immunity as well as normal tissue
homeostasis.
 Cell signaling is a process through which living cells interact with the cellular
environment and neighbouring cells.
 Intracellular signalling is the key to the evolution of multi-cellular organism.
 This involves determining the function of the individual cells within the context of
the organism as well as the response of specific cells or group of cells to the
environment.

5. Importance of Signals
Intracellular signalling is essential to the survival of organisms providing opportunity
to adapt suitability. Following important functions may be attributed:
 Maintenance of homeostasis
 Control of cell division and cell death
 Adaptation to environmental conditions
 Control of development and growth
 Release and production of hormones and other regulatory molecules
 Response elicited between organisms- including establishment of pathogenesis,
activation of defences, establishment of symbiosis etc.

6. Signal Transduction
 Signalling refers to the process by which cells release, receive , propagate and
respond to information from their environment and from each other .
 It is an important part of cell signalling process and refers to the conversion of a
signal from one form to another .
 The receptor transmits the signal across the membrane , converting the
extracellular signal to an intracellular signal.
 In most cases, additional proteins and small molecules participate in relaying the
message to its ultimate destination in the cell where a response is evoked .
 The response could be any imaginable cellular activity. However, many drugs
interfere or exacerbate the responses to signalling pathways.

7. Steps in signalling
1) Biosynthesis and release of the signal
2) Transport of signal to target cell
3) Transduction in target cell
4) Alteration of cell growth and
metabolism pertaining to response.
5) Termination of signal

8. Categories of Signalling

9. Paracrine or Local Signalling
Signalling molecules are released from
paracrine cells and diffuse locally through
the extracellular fluid, targeting cells that
are nearby, thus acting as local mediators .
Many of the cells that are involved in
inflammation during infection, or that
regulate cell proliferation utilise this type
of signalling. For example cancer cells
sometimes enhance their own survival or
proliferation in this way. Examples of
signalling molecules that often function in
a paracrine manner include transforming
growth factor-β (TGF-β) and fibroblast
growth factors (FGFs).

10. Neuronal signalling : special case of
paracrine
Nerve cells (neurons) are specialised cells with a
unique structure that can send signals very
quickly, over long distances and to specific
target cells. A signal is detected by receptors
present on dendrites and then carried along the
axon to a presynaptic terminal. When the signal
reaches the presynaptic terminal, vesicles
containing signalling molecules
(neurotransmitters) fuse with the membrane,
releasing the contents into the synaptic space .
These neurotransmitters are detected by
receptors on the postsynaptic membrane i.e.
the cell membrane of the target cell, which may
be another neuron or an effector
cell. Examples of neurotransmitters
include acetylcholine, serotonin and histamine.

11. Endocrine or Long distant signalling
This is the most common type of cell
signaling and involves sending a signal
throughout the whole body by secreting
hormones into the bloodstream of animals
or the sap in plants . The cells that produce
hormones in animals are called endocrine
cells. For example, the pancreas is an
endocrine gland and produces the
hormone insulin, which regulates the
uptake of glucose in cells all over the body.
Examples of hormones that function in
an endocrine manner include testosterone,
progesterone and gonadotropins.

12. Autocrine or Self signalling
Autocrine signalling is important in
immune system and it also frequently
contributes to uncontrolled growth of
cancer cells. In the situation cancer cells
produce a factor to which they respond,
deriving their own unregulated
proliferation.

13. Juxtacrine or Contact-dependent
signalling
 This does not involve the release of secreted
molecules and only occurs over short distances.
The cells make direct physical contact through
signal molecules found in the plasma
membrane of the signalling cells and receptor
proteins present in the plasma membrane of
the target cell. This type of signalling is
extremely important during embryonic
development and cell-fate determination (when
similar cells that are close to each other
specialise to form a specific cell type). The
Notch pathway mediates juxtacrine signalling
between adjacent cells Notch receptors are
single transmembrane proteins and they bind
to specific ligands on adjacent cells. Ligand
binding results in proteolytic cleavage of the
Notch receptor which releases an intracellular
domain that is translocated to the nucleus
where it regulates gene expression.

14. Types of Receptors
Receptors are protein molecules in the target cell or on its surface that bind
ligands. There are two types of receptors: internal receptors and cell-surface
receptors.

15. Internal Receptors
Internal receptors, also known as intracellular or
cytoplasmic receptors, are found in the cytoplasm of
the cell 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 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 that ultimately forms a protein. When
the ligand binds to the internal receptor, a
conformational change exposes a DNA-binding site
on the protein. The ligand-receptor complex moves
into the nucleus, binds to specific regulatory regions
of the chromosomal DNA, and promotes the
initiation of transcription. Internal receptors can
directly influence gene expression without having to
pass the signal on to other receptors or messengers.

16. Cell surface receptors
Cell-surface receptors, also known as
transmembrane receptors, are cell surface,
membrane-anchored, or 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.

17. Cell surface receptors
 Each cell-surface receptor has three main components: an external ligand-binding
domain (extracellular domain), a hydrophobic membrane-spanning region, 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.

18. Ion channel-linked receptors
Ion channel-linked receptors bind a ligand and
open a channel through the membrane that
allows specific ions to pass through. To form a
channel, this type of cell-surface receptor has an
extensive membrane-spanning region. In order
to interact with the phospholipid fatty acid tails
that form the center of the plasma membrane,
many of the amino acids in the membrane-
spanning region are hydrophobic in nature.
Conversely, the amino acids that line the inside
of the channel are hydrophilic to allow for the
passage of water or 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, and hydrogen to pass through.

19. G- protein linked receptors
 G-protein-linked receptors bind a ligand and activate a
membrane protein called a G-protein. The activated G-
protein then interacts with either an ion channel or an
enzyme in the membrane. All G-protein-linked receptors
have seven transmembrane domains, but each receptor
has its own specific extracellular domain and G-protein-
binding site.
 Cell signaling using G-protein-linked receptors occurs as
a cyclic series of events. Before the ligand binds, the
inactive G-protein can bind to a newly-revealed site on
the receptor specific for its binding. Once the G-protein
binds to the receptor, the resultant shape change
activates the G-protein, which releases GDP and picks
up GTP. The subunits of the G-protein then split into the
α subunit and the β subunit. One or both of these G-
protein fragments may be able to activate other
proteins as a result. Later, the GTP on the active α
subunit of the G-protein is hydrolyzed to GDP and the β
subunit is deactivated. The subunits reassociate to form
the inactive G-protein, and the cycle starts over.

20. 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 or the enzyme-linked
receptor has an intracellular domain that interacts
directly with an enzyme. The enzyme-linked receptors
normally have large extracellular and intracellular
domains, but the membrane-spanning region consists of
a single alpha-helical region of the peptide strand. When
a ligand binds to the extracellular domain, a signal is
transferred through the membrane and activates the
enzyme, which sets off a chain of events within the cell
that eventually leads to a response. An example of this
type of enzyme-linked receptor is the tyrosine kinase
receptor. The tyrosine kinase receptor transfers
phosphate groups to tyrosine molecules. Signalling
molecules bind to the extracellular domain of two
nearby tyrosine kinase receptors, which then dimerize.
Phosphates are then added to tyrosine residues on the
intracellular domain of the receptors and can then
transmit the signal to the next messenger within the
cytoplasm.

21. Receptor Tyrosine Kinases
 Receptor Tyrosine Kinases (RTKs) are another class of receptors revealed to show
unforeseen diversity in their actions and mechanisms of activation. The general
method of activation follows a ligand binding to the receptor tyrosine kinase,
which allows their kinase domains to dimerize. This dimerization then invites the
phosphorylation of their tyrosine kinase domains that, in turn, allow intracellular
proteins to bind the phosphorylated sites and become “active.” An important
function of receptor tyrosine kinases are their roles in mediating growth pathways
(i.e., Epidermal Growth Factors, Fibroblast Growth Factors). Of course, the downside
of having complex signaling networks lies in the unforeseen ways in which any
alteration can produce disease or unregulated growth – cancer.

22. Thank you