Cell signalling system

3. • Cells communicate with other cells
and with their external environment
through signal mechanisms.
• Cellular communication- to
coordinate the activities needed for
an organism
»Grow
»Develop & function.

14. CONTACT DEPENDENT
SIGNALLING
• Signal molecules remain bound to the surface
of the signalling cell & influence cells that are
in contact with it.
• Eg: immune response, development

17. SYNAPTIC SIGNALLING
• Specialised paracrine signalling occurring within cells
of nervous system.
• Eg: Neurotransmitters
• Released at the axon end of a nerve cell traverse the
synaptic cleft to the target cells (neurons, muscle).
• Very fast signalling.
• Action: neurotransmitter diffuse across synaptic cleft
bind to the receptor on the next
neuron/muscle

25. Ligands or signalling molecules
• Cells in multicellular organisms communicate by using signalling molecules
• Ligands : Signaling molecules that bind receptors.
• Eg: small peptides, amino acids, proteins, nucleotides, retinoids, steroids,
fatty acid derivatives or even nitric oxide or carbon monoxide.
• In most cases signal molecules get out from the cell by exocytosis.
• Some molecules are released by diffusion through the plasma membrane
and some remain bound to the surface of the cell.
• Signal molecules or ligands binds to specific site on its receptor.
• Ligands may be large or small and polar or non-polar.
• Large or polar signal molecules cannot move through membranes and so
are generally bound by receptor molecules attached to the cell membrane.
• Small or non-polar ligands, diffuse through membranes and so may be
received by receptor molecules in the cytoplasm.

26. Ligands or signalling molecules
Hormones
Cytokines & Growth factors
Vitamin A & D derivatives
Nitric Oxide

27. Molecules in signaling
1. Hormones
• Hormones are regarded as 'classical' signaling molecules.
• Hormones are produced by endocrine glands (Pancreas,
thyroid gland, Gonads) which secrete the hormones
into the circulation. They reach their target cells that are
even distant from the secreting gland.
• Target cells have specific receptors that pick up the
signal.
• Steroid hormones (Estrogen, Testosterone) and peptide
hormones (Insulin, glucagon) take different signaling
pathways.

28. 2. Cytokines and growth factors
• Cytokines and growth factors are regulatory
proteins or peptides secreted by many cell types.
• Most cytokines or growth factors are paracrine in
their action.
• They diffuse short distance to act only on local
cells, while some are autocrine in action.
• Eg: Cytokines includes interleukin(IL), tumour
necrosis factor (TNFS) & interferons.
• They act in a paracrine or autocrine fashion.
• Cytokines are specific receptors on the cell surface
to which they bind.

29. 3. Vitamin A and D derivatives
• Retinoic acid derived from vitamin A.
• Important as a signaling molecule in embryonic
development and normal cell growth.
• Vitamin D3 is involved in control of genes
involved in calcium absorption from the
intestine.
• These signalling molecules act on target cells
by binding intracellular receptors after entering
the cell by diffusion across the plasma
membrane.

30. 4. Nitric oxide
• Nitric oxide is a simple gas synthesized from the amino
acid L-arginine by the enzyme nitric oxide synthase.
• It acts as a paracrine signaling molecule in the nervous,
immune, and circulatory systems.
• Extremely unstable and acts locally to affect nearby cells.
• Like steroids they diffuse across the plasma membrane
of its target cell and instead of binding to a receptor, it
regulates the activity of intracellular target enzymes.
• Nitric oxide increases the activity of the second
messenger cyclic guanosine monophosphate (cGMP) in
smooth muscle cells, which then causes muscle cell
relaxation and blood vessel dilation.

31. Receptors
• Receptors are generally proteins or glycoproteins.
• Present on target cells that bind the signal molecule and begins
the response process within the target cell.
• Receptors might be located in the plasma membrane or within
the cytoplasm of the cell.
• In most cases the receptors that recognise the signal molecules
are transmembrane proteins on the surface of the target cell.
• Binding of a ligand causes a conformational or shape change
in the receptor molecule, it becomes active and produces a set
of intracellular signals.
• In some cases the receptors are located inside the target cell, so
that signal molecules have to be small enough to diffuse
through the plasma membrane.

33. Cell surface receptors
• When a cell-signalling molecule binds to a
specific cell surface receptor, it activates a
series of intracellular targets located
downstream of the receptor.

34. Ion-channel-linked receptors
• These are transmembrane protein acting as
ion-channels temporarily opened and closed
by a small amount of neurotransmitter binding
to them.
• This changes the ion permeability of the
plasma membrane as well as the excitability of
the post synaptic cell.

35. G-protein -coupled receptor (Guanine-nucleotide-
binding proteins)
• When a signalling molecule binds to the
extracellular portion of a cell surface
receptor, its cytosolic domain undergoes
conformational change that enables binding of
the receptor to a G protein.
• This activates the G protein, which then
dissociated and triggers an intracellular signal
to an enzyme.

37. Tyrosine kinases as receptor proteins
• These surface receptors are enzymes that
phosphorylates substrate proteins on tyrosine residues.
• Binding of a ligand (growth factor) to the
extracellular domain of these receptors induces
receptor dimerization that results in receptor
autophosphorylation (two polypeptide chains
phosphorylate one another).
• This determines the binding of the tyrosine kinase
domain to the down stream signaling molecules.

39. Intra cellular receptors
• Many lipid soluble hormones diffuse across the plasma
membrane and interact with receptors in the cytosol or
nucleus.
• Resulting hormone receptor complexes bind to transcription-
control regions in DNA thereby affecting expression of specific
genes.
• Hormones of this type include the steroids, thyroxin and retinoic
acid.
• Eg: Steroid hormones after crossing the plasma membrane interact
with intracellular receptors forming complexes that can increase
or decrease transcription of specific genes.

41. Intracellular Signalling Pathways
• Cell surface receptors stimulate intracellular target enzymes that
are directly or indirectly coupled to receptors by G proteins.
• These enzymes serve as downstream signalling elements that
propagate and amplify the signal initiated by ligand binding.
• This involves a process called intracellular signal transduction
which consists of a chain of reactions for transmitting the signal
from the cell surface to intracellular targets.
• The targets frequently include transcription factors that functions
to regulate gene expression.
• Intracellular signaling pathways connect the cell surface to the
nucleus, leading to changes in gene expression in response to
extracellular stimuli.

53. Ca2+
-phosphotidyl inositol pathway
• Another second messenger involved in intracellular signaling is derived from
the membrane phospholipid phosphatidylinositol 4,5 Disphosphate
(PIP )
₂ .
• A variety of hormones and growth factors stimulate the hydrolysis of PIP₂,
which leads to the production of two distinct second messengers
diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3).
• Diacylglycerol remains associated with plasma membrane and activates
members of protein kinase C family (protein-serine/threonine kinase), which
plays an important role in the control of cell growth and differentiation.
• The other second messenger, IP3, is released into the cytosol and acts to
signal the release of Ca²+
from intracellular stores.
• Increased cytosolic Ca²+
level affects the activities of a variety of target
proteins, including protein kinases and phosphatases.

57. Ras-Raf-MAP Kinase
Pathway