سلولها می‌توانند به یکدیگر سیگنال بدهند و سیگنالهایی را که از سلولهای دیگر و محیط دریافت می کنند، تفسیر کنند. سیگنالها ممکن است شامل نور و یا بر اثر تماس باشند، اما اغلب مواد شیمیایی هستند. در این جلسه، ما بر مکانیسم های اصلی انتقال پیام متمرکز می‌شویم که سلولها سیگنال‌های شیمیایی ارسال شده از سلولهای دیگر را دریافت، پردازش و پاسخ می‌دهند.
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Cells can signal to each other and interpret the signals they receive from other cells and the environment. The signals may include light and touch, but are most often chemicals. In this session, we focus on the main mechanisms by which cells receive, process, and respond to chemical signals sent from other cells.
2. Outlines
• The nature of signaling
• The elements of signaling
• Types of signaling
• Stages of signaling
• Reception: A signaling molecule binds
to a receptor protein
• Plasma membrane receptors
• G protein-coupled receptors
• Receptor Tyrosine Kinases
• Ion channel receptors
• Intracellular receptors
• Transduction
• Response
3. The Elements of Signaling
• Signaling pathway is composed of
different elements:
• Signaling cell
• Signal
• Target cell
• Signal transduction: is the conversion of
one form of signal to another
• Cell signaling: is receiving and
transducing signals
4. Types of signaling
• The released signal may carry out its
effect on:
• Local cells (local signaling)
• Distant cells (long-distant signaling)
• In both animal and plant:
• Cell junctions
• Cell-cell recognition
• AKA Contact-dependent
6. Stages of signaling
• There are 3 stage:
• Reception: Reception is the target
cell’s detection of a signaling molecule
coming from outside the cell.
• A chemical signal is “detected” when the
signaling molecule binds to a receptor
protein located at the cell’s surface
• Transduction: converts the signal to a
form that can bring about a specific
cellular response.
• Response: the transduced signal finally
triggers a specific cellular response.
8. Reception
• Main elements of this system are:
• Receptor protein molecule
• Ligand molecule
• Ligand binding generally causes a
receptor protein to undergo a
change in shape.
• 3 types of receptors are involved
in this stage:
• G protein-coupled receptors (GPCR)
• Receptor Tyrosine Kinases (RTKs)
• Ion channel receptors
9. Reception – G protein receptors
• A G protein-coupled receptor
(GPCR) is a cell-surface
transmembrane receptor that works
with the help of a G protein, a
protein that binds the energy-rich
molecule GTP.
11. Reception – RTKs
• Receptor tyrosine kinases
(RTKs) belong to a major class
of plasma membrane
receptors characterized by
having enzymatic activity.
13. Reception – Ion channel Receptors
• A ligand-gated ion channel is a type
of membrane channel receptor
containing a region that can act as a
“gate,” opening or closing the
channel when the receptor changes
shape.
• When a signaling molecule binds as
a ligand to the channel receptor, the
channel opens or closes, allowing or
blocking the flow of specific ions,
such as Na+ or Ca2+.
17. Transduction
• Signal transduction pathway is the
chain of molecular interactions that
leads to a particular response within
the cell.
• Like dominos, it resembles a series of
activations
• Transduction molecules:
• Proteins
• Phosphorylation/ Dephosphorylating
• Small Molecules and Second
Messengers
• Cyclic AMP (cAMP)
• Calcium ion and Inositol Triphosphate
(IP3)
18. Transduction Proteins
• Protein Phosphorylation and
Dephosphorylation
• Protein Kinase:
• An enzyme that transfers phosphate
groups from ATP to a protein
• Protein Phosphatase:
• An enzymes that can rapidly remove
phosphate groups from proteins
19. Signaling – Transduction Small Molecules
• Cyclic AMP
• The second messenger cyclic AMP
(cAMP) is made from ATP by
Adenylyl Cyclase
• This enzyme is embedded in the
plasma membrane.
• The phosphate group in cAMP is
attached to both the 5’ and the 3’
carbons; this cyclic arrangement is
the basis for the molecule’s name.
• Cyclic AMP is inactivated by
phosphodiesterase
• This enzyme converts it to AMP.
20. Signaling – Transduction Small Molecules
• Cyclic AMP
• Epinephrine and many other signaling
molecules lead to activation of adenylyl
cyclase by G proteins and formation of
cAMP
• The immediate effect of an elevation in
cAMP levels is usually the activation of a
serine/threonine kinase called protein
kinase A.
21. Transduction Small Molecules
• Calcium Ions and Inositol
Trisphosphate (IP3 )
• In animals many signaling molecules
induce responses their target cells via
increasing the cytosolic concentration
of calcium ions (Ca2+):
• Neurotransmitters
• Growth factors
• Some hormones
22. Transduction Small Molecules
• The Ca2+ concentration in the cytosol is
usually much lower than in the
extracellular fluid and ER.
• Protein pumps in the plasma membrane
and the ER membrane, driven by ATP, move
Ca2+ from the cytosol into the
extracellular fluid and into the lumen of
the ER.
• Mitochondrial pumps, driven by
chemiosmosis, move Ca2+ into
mitochondria when the calcium level in the
cytosol rises significantly.
23. Transduction Small Molecules
• If the cytosolic Ca2+ level is low, in
response to a signal relayed by a signal
transduction pathway, the cytosolic
calcium level may rise, usually by a
mechanism that releases Ca2+ from
the cell’s ER.
• The pathways leading to calcium
release involve two other second
messengers:
• Inositol trisphosphate (IP3)
• Diacylglycerol (DAG).
• Scientists use the term second
messenger for all small, non-
protein components of signal
transduction pathways.
25. Response
• The response at the end of the
pathway may occur:
• In the nucleus: Many signaling pathways
ultimately regulate protein synthesis, usually
by turning specific genes on or off in the
nucleus. Like an activated steroid receptor,
the final activated molecule in a signaling
pathway may function as a transcription
factor.
• In the cytoplasm: Sometimes a signaling
pathway may regulate the activity of proteins
rather than causing their synthesis by
activating gene expression. This directly
affects proteins that function outside the
nucleus
26. Summary
• The nature of signaling
• The elements of signaling
• Types of signaling
• Stages of signaling
• Reception: A signaling molecule binds
to a receptor protein
• Plasma membrane receptors
• G protein-coupled receptors
• Receptor Tyrosine Kinases
• Ion channel receptors
• Intracellular receptors
• Transduction
• Primary element: Proteins
• Secondary elements:
• Small molecules: cAMP
• Ions: Ca2+
• Response
• In the nucleus
• In the cytoplasm
