Cell-Cell Signaling - Masika 2021

Cell Communication
DR. MASIKA
Department of Medical Physiology
2021
The Cellular Internet
• Cell-to-cell communication
-Is absolutely essential for multicellular
organisms
- External signals are converted into responses
within the cell
Communication between cells requires
- Ligand : the sgnaling molecule
- Receptor protein: the molecule to which the

receptor binds (may be on the plasma
membrane or within the cell).
Evolution of Cell Signaling
Yeast cells
Identify their mates by cell signaling
1  factor
Exchange of
mating factors. Receptor
Each cell type
secretes a
mating factor a 
that binds to
receptors on
the other cell
type.  factor
Yeast cell, Yeast cell,
mating type a mating type 
2 Mating. Binding
of the factors to
receptors
induces changes a 
in the cells that
lead to their
fusion.
3New a/ cell.

The nucleus of
the fused cell
includes all the
a/
genes from the
a and a cells.
Cell Communication
There are four basic mechanisms for cellular
communication:
1. direct contact
2. paracrine signaling
3. endocrine signaling
4. synaptic signaling
Cell
Direct contact
Communication
– molecules on the surface of one cell are recognized
by receptors on the adjacent cell
Cell Communication
Paracrine signaling
– signal released from a cell has an effect on
neighboring cells
Cell Communication
Endocrine signaling (long distance signaling)
– hormones released from a cell affect other cells
throughout the body
Cell Communication
Synaptic signaling
– nerve cells release the signal (neurotransmitter) which
binds to receptors on nearby cells
The Three Stages of Cell Signalin
suggested by Earl W. Sutherland
Cells receiving signals go through three

processes:
- Reception
- Transduction
- Response
Overview of cell signaling
EXTRACELLULAR CYTOPLASM
FLUID Plasma membrane
1 Reception 2 Transduction 3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Signal
molecule
Signal Reception
• A signal molecule( ligand) binds to a receptor protein,
causing it to change shape
• The binding between signal molecule (ligand)

– And receptor is highly specific
• A conformational change in a receptor

– Is often the initial transduction of the signal
signal transduction: the cascade of events within the cell that

occur in response to a signal
Different cell types can respond differently to the same signal.

Cell Communication
• A cell’s response to a signal often involves activating or
inactivating proteins.
• Phosphorylation is a common way to change the activity of

a protein.
protein kinase
– an enzyme that adds a phosphate to a protein
phosphatase
– an enzyme that removes a phosphate from a protein
Receptor Types
Receptors can be defined by their location.
• intracellular receptor
– located within the cell ( are cytoplasmic or nuclear proteins)
• Signal molecules that are small or hydrophobic

– And can readily cross the plasma membrane
use these receptors
Extracellular receptors
• cell surface receptor or membrane receptor

– located on the plasma membrane to bind a ligand outside the
cell
Receptor Types
There are 3 subclasses of membrane
receptors:
1. channel linked receptors – ion channel
that opens in response to a ligand
2. enzymatic receptors – receptor is an
enzyme that is activated by the ligand
3. G protein-coupled receptor – a G-
protein (bound to GTP) assists in
transmitting the signal
Intracellular Receptors
steroid hormones
-have a nonpolar, lipid-soluble structure
-can cross the plasma membrane to a
steroid receptor
-usually affect regulation of gene expression
An inhibitor blocks the receptor from binding

to DNA until the hormone is present.
Intracellular Receptors
A steroid receptor has 3 functional domains:
1. hormone-binding domain
2. DNA binding domain
3. domain that interacts with coactivators to
affect gene expression
Receptor Kinases
receptor tyrosine kinases
-membrane receptor
-when bound by a ligand, the receptor is
activated by dimerization and
autophosphorylation
-activated receptor adds a phosphate to
tyrosine on a response protein
-an example is the insulin receptor
Receptor Kinases
kinase cascade – a series of protein
kinases that phosphorylate each other in
succession
-amplifies the signal because a few signal
molecules can elicit a large cell response
mitogen-activated protein (MAP) kinases

are activated by kinase cascades
G-Protein Coupled Receptors
G-protein – protein bound to GTP
G-protein-coupled receptor (GPCRs) –
receptors bound to G proteins
-G-protein is a switch turned on by the
receptor
-G-protein then activates an effector protein
(usually an enzyme)
G-Protein Coupled Receptors
Once activated, the effector protein
produces a second messenger.
-second messenger generates the cellular
response to the original signal
For example – one common effector protein
is adenylyl cyclase which produces
cAMP as a second messenger.
Other second messengers: inositol
phosphates, calcium ions (Ca2+)
Cell-to-Cell Interactions
Cells can identify each other by cell surface
markers.
-glycolipids are commonly used as tissue-
specific markers
-major histocompatibility complex (MHC)
proteins are used by cells to distinguish
“self” from “non-self”
Cell-to-Cell Interactions
Cells within a tissue are connected to each
other by cell junctions
1. tight junctions – create sheets of cells
2. anchoring junctions – connect the
cytoskeletons of adjacent cells
3. communicating junctions – permit small
molecules to pass between cells
a. gap junctions – in animal cells
b. plasmodesmata – in plant cells

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Cell Communication

- Receptor protein: the molecule to which the

3New a/ cell.

Cells receiving signals go through three

1 Reception 2 Transduction 3 Response

Relay molecules in a signal transduction pathway

• The binding between signal molecule (ligand)

• A conformational change in a receptor

signal transduction: the cascade of events within the cell that

Different cell types can respond differently to the same signal.

• Phosphorylation is a common way to change the activity of

• Signal molecules that are small or hydrophobic

• cell surface receptor or membrane receptor

An inhibitor blocks the receptor from binding

mitogen-activated protein (MAP) kinases

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