Intercellular Communication

&
Signal Transduction Mechanism

Department of Physiology
School of Medicine
University of Sumatera Utara
 Intercellular Communication
and Signal Transduction

The ability of cells to communicate

with each other is essential for
coordination of their diverse
activities to maintain homeostasis as
well as to control growth and
development of the body as a whole
 Intercellular Communication
and Signal Transduction
These signals come from distant cells
(known as endocrine signals, like
hormones and growth factors); they
come from neighboring cells (known
as paracrine signals); they even come
from within the same cell (known as
autocrine signals)
 Signaling Types
Local signaling
 Gap junction
 Paracrine--signaling that affects
neighboring cells
 Autocrine--secretion that affects same cell

Long Distance
 Endocrine--secretion of a substance that is
released into the blood and affects a
distant target
 Gap Junction

A gap junction or nexus is a junction

between certain cell-types that allows
different molecules and ions to pass freely
between cells.

The junction connects the cytoplasm of

cells. One gap junction is composed of two
connexons (or hemichannels) which
connect across the intercellular space.
 Gap Junction
At gap junctions, the intercellular spaces narrows from 2nm to 3nm
and unit connexons in the membrane of each cell are lined up with one
another
 Gap Junction
Allows for chemical communication
between cells, through the transmission of
small second messengers, such as Ca++,
although different connexin subunits can
make selectivity for particular small
molecules.

Generally allows molecules smaller than

1,000 Daltons to pass through,
 Gap junctions are particularly
important in the cardiac muscle: the
signal to contract is passed
efficiently through the gap junctions,
allowing the heart muscle cells to
contract in tandem.
Paracrine

The signal chemical is

called the paracrine
agent.
They are secreted into
the interstitial fluid
and diffuse to
adjacent cells, where
they have their
biologic action
Paracrine
 Autocrine

Autocrine is a form of hormonal

signalling in which a cell secretes a
hormone, or chemical messenger
(called the autocrine agent) that binds
to autocrine receptors on the same cell,
leading to changes in the cell
Autocrine
 The endocrine system

The other communication system in

the body is made up of endocrine
glands that produce hormones,
chemical substances released into
the bloodstream to guide such
processes as metabolism, growth, etc.
 The endocrine system

The endocrine system is an

information signaling system much
like the nervous system. However,
the nervous system uses nerves to
conduct information, whereas the
endocrine system uses blood vessels
as information channels
 The endocrine system
Glands located in many regions of the body
release into the bloodstream specific
chemical messengers called hormones,
which regulate the many and varied
functions of an organism.
 The endocrine system
The typical endocrine organ is a ductless
gland that secretes chemical mediators
directly into local blood vessels which
circulate within the body via the
bloodstream. These hormones travel to
distant organs to regulate the target
organ's function.
The endocrine system

Major endocrine glands. (Male

left, Female on the right.)
1. Pineal gland
2. Pituitary galnd
3. Thyroid galnd
4. Thymus
5. Adrenal gland
6. Pancreas
7. Ovary
8. Testes
The endocrine system
 Intercellular Communication
and Signal Transduction
Gap Synaptic Paracrine & Endocrine
junctions Autocrine
Message Directly Across By diffusion By
transmission from cell synaptic in interstitial circulating
to cell cleft fluid body fluids
Local or Local Local Locally General
general diffused
Specificity Anatomic Anatomic Receptors Receptors
depends on location location &
receptors
 Signal Transduction in Cells

Cells in our body are surrounded by a

lipid membrane. The "water-loving"
heads of the phospholipid molecules
(blue) are directed towards the outer
and inner surfaces of the membrane.
Many proteins stretch through the entire
membrane.
Signal Transduction in Cells
Extracellular signaling molecules
(usually hormones, neurotransmitters,
cytokines, growth factors or cell
recognition molecules) attach to the
receptor, triggering changes in the
function of the cell
The binding initiates a chemical
change on the intracellular side of the
membrane
 Signal Transduction in Cells
Extracellular signal molecule: an extracellular signal
molecule is produced by one cell and is capable of traveling
to neighboring cells, or to cells that may be far away.

Receptor protein: the cells in an organism must have cell

surface receptor proteins that bind to the signal molecule
and communicate its presence inward into the cell.

Intracellular signaling proteins: these distribute the signal to

the appropriate parts of the cell. The binding of the signal
molecule to the receptor protein will activate intracellular
signaling proteins that initiate a signaling cascade (a series
of intracellular signaling molecules that act sequentially).

Target proteins: the conformations or other properties of the

target proteins are altered when a signaling pathway is
active and changes the behavior of the cell
 Signal Transduction in Cells
A first messenger (1), a molecule of adrenaline,
binds to a specific adrenaline receptor (2), a
discriminator. Thereby, the transducer (3), a G
protein - composed of alpha-, beta- and gamma
subunits - is activated, This, in turn, stimulates the
amplifier (4), adenylate cyclase, which produces (5)
the second messenger, cyclic AMP, from (6) ATP
(adenosine- triphosphate).
(7) A cascade of enzymatic reactions alters the
behaviour of the cell and (8) via phosphorylation (9)
glycogen is transformed to (10) glucose, which the
cell uses to generate ATP.
Phosphorylation can also alter membrane proteins,
for example, ion channels (11)
 Signal Transduction in Cells
Activation and Inactivation of the G Protein

1. The G protein, composed of alpha-, beta- and

gamma-subunits, in its resting state with bound GDP
 Signal Transduction in Cells
Activation and Inactivation of the G Protein

2. The receptor with bound hormone activates

the G protein and replaces GDP...
 Signal Transduction in Cells
Activation and Inactivation of the G Protein

3. ...with GTP and the G proteins is

activated. The subunits separate.
 Signal Transduction in Cells
Activation and Inactivation of the G Protein

4. Some seconds later the GTP, bound

to the alpha-subunit, is hydrolysed to
GDP. The subunits recombine.
 Membrane receptors

specialized integral membrane proteins

that take part in communication
between the cell and the outside world

play a unique and important role in

cellular communications and signal
transduction
 Membrane receptors

Membrane receptors generally function

by binding the signal, or ligand and
causing the production of a second
signal (second messenger) that causes
a cellular response. The diagram shows
how the receptor for insulin functions.
Membrane receptors
A pair of insulin molecules bind to
receptors, causing a change in the
protein structure that exposes a
kinase or phosphate transferring
enzyme inside the cell
The activated receptor kinase
transfers a phosphate group to
adjacent receptor molecules,
leading to the activation of
subcellular proteins and a cellular
response to insulin
The receptors must be integral
membrane proteins that pass
through the lipid bilayer. Through
this system, an insulin molecule can
cause a response inside the cell
without passing through the lipid
bilayer
Cellular response