modes of cell signalling
Cell signaling can result either from the direct interaction of a cell with its
neighbor or from the action of secreted signaling molecules. Signaling by
direct cell–cell (or cell–matrix) interactions plays a critical role in
regulating the behavior of cells in animal tissues. cell expresses variety of
cell surface receptors that interact with signalling molecules on surface of
neighboring cells.
signaling by secreted molecules are divided into three general
categories based on the distance over which signals are
transmitted.
1. endocrine signaling ; the signaling molecules (hormones) are
secreted by specialized endocrine cells and carried through the
circulation to act on target cells at distant body sites.
Example; steroid hormone estrogen, which is produced by the
ovaries and stimulates development and maintenance of the
female reproductive system and secondary sex characteristics.
In animals, more than 50 different hormones are produced by
endocrine glands, including the pituitary, thyroid, parathyroid,
pancreas, adrenal glands, and gonads.
2. paracrine signaling ; a molecule released by one cell acts on
neighboring target cells.
example ; action of neurotransmitters in carrying signals
between nerve cells at a synapse. Finally, some cells respond
to signaling molecules that they themselves produce.
3. autocrine signaling ; is the response of cells of the vertebrate
immune system to foreign antigens.
Certain types of T lymphocytes respond to antigenic
stimulation by synthesizing a growth factor that drives their
own proliferation, thereby increasing the number of
responsive T lymphocytes and amplifying the immune
response.
abnormal autocrine signaling frequently contributes to the
uncontrolled growth of cancer cells . In this situation, a cancer
cell produces a growth factor to which it also responds,
thereby continuously driving its own unregulated
proliferation .
Modes of cell–cell signaling Cell
signaling can take place
either through (A) direct cell–cell
contacts or (B) the action of
secreted signaling molecules. In
endocrine signaling, hormones are
carried through the circulatory
system to act on distant target cells.
In paracrine signaling, a molecule
released from one cell acts locally
to affect nearby target cells. In
autocrine signaling, a cell produces
a signaling molecule to which it also
responds.
Receptor
A receptor is a molecule that receives signals (chemical or hormonal)
from outside the cell and is usually located on the cell surface .
Receptors are proteins that undergo a conformational change upon
attachment of their corresponding signaling molecule, which in turn
induces a chain reaction (also known as signal transduction) within
the cell leading to various cellular responses, including cell death.
The signaling molecule that binds to the receptor (also known as a
ligand) can be a peptide, a hormone, neurotransmitter drug, toxin,
etc.
Each receptor possesses 2 functional domains: the recognition
domain which binds ligands and the coupling domain which is
involved in signal transduction.
Cell Surface Receptors
Cell surface receptors are transmembrane proteins embedded into the
plasma membrane which play an essential role in maintaining
communication between the internal processes within the cell and
various types of extracellular signals.
Such extracellular signals include hormones, cytokines, growth
factors, neurotransmitters, lipophilic signaling molecules such as
prostaglandins, and cell recognition molecules.
When any of these ligands bind to their corresponding receptor, a
conformational change is triggered which initiates an intracellular
signaling pathway.
Each ligand has its own specific cell surface receptor. Cell surface
receptors have the following components/domains:
• The extracellular domain which binds ligands and is exposed to the
outer surface of the cell; also known as the recognition domain.
• The membrane-spanning region made up of hydrophobic protein
molecules
• The intracellular domain which is in contact with the cytoplasm; also
known as the coupling domain.
Types ; Cell surface receptors are generally classified into the
following categories:
1. Ligand-gated ion channel-linked receptors
2. Enzyme-linked receptors
3. G-protein-linked receptors
4. lon channel-linked receptors
1. ligand gated ion channel linked receptors ;
These are the cell receptors that are at the cell membrane. These
are the channel-like structure.
Whenever there is a ligand attached to it. It will open its channel.
Using this channel, ions will exchange there.
As it is a cell surface receptor. So, its Ligand Binding Domain is on
the outside of the cell. There the ligand will attach to it. It helps to
move in or out of the Na +, K+, etc.
These types of receptors are often found in Skeleton Muscles. It has
a heteromeric structure. .
EXAMPLE ; Acetylcholine chemical will bind with the receptor. As a
result, the channel will be opened. And the ions will be exchanged
there. This is found in the skeleton muscles .
2 . Enyzme linked receptor:
Enzyme-linked receptors are typically single-pass transmembrane
proteins that act as enzymes or are associated with enzymes.
Enzyme-linked receptors have both an extracellular binding site for
chemical signaling and an intracellular domain whose catalytic
action is controlled by the binding of an extracellular ligand and are
thus also called catalytic receptors.
There are 6 types of enzyme-linked There are 6 types of enzyme-
linked receptors:
Receptor tyrosine kinases which phosphorylate specific tyrosine
residues on specific intracellular signaling proteins (EGFR); they
bind to polypeptide growth factors which are responsible for
controlling cell proliferation and differentiation.
Tyrosine-kinase-associated receptors which are enzymes that
associate with intracellular proteins that have tyrosine kinase
activity (Cytokines)
Receptor-like tyrosine phosphatases which remove phosphate
groups from tyrosines of their target intracellular proteins.
Receptor serine/threonine kinases which phosphorylate specific
serines or threonines on associated generegulatory proteins.
Receptor guanylyl cyclases which directly catalyze the production
of cyclic GMP in the cytosol (natriuretic peptide receptor).
Histidine-kinase-associated receptors which activate a 2-
component signaling pathway where the kinase phosphorylates
itself on histidine residues (autophosphorylation) and then
immediately transfers the phosphate to a second intracellular
protein; not present in animal cellsG-protein linked receptors
3 . G-protein-coupled receptors (GPCRs) ; are the largest cell surface
receptors, composed of 7 transmembrane proteins in the plasma
membrane.
GPCRs are responsible for activating the trimeric membrane-
bound G-proteins (GTP binding proteins) which subsequently
activate either an ion channel (effector) or an enzyme in the
cell membrane.
G-proteins proteins function as an intermediate transducer
molecule that plays a vital role in regulating intracellular
functions through a secondary mechanism which is in turn
activated by G-protein coupled receptors.
Many different types of G-protein-coupled receptors are
known, such as the acetylcholine (Ach) receptor, B- adrenergic
receptor, metabotropic glutamate receptors, certain olfactory
receptors, receptors for peptide hormones, and rhodopsin (a
photosensitive receptorMany neurotransmitters,
neuropeptides, peptide hormones, as well as a number of
others can activate G-protein coupled receptors.
GPCRs are responsible for targeting various signaling pathways,
including sensory perception such as sight, taste, smell, and
pain sensations. GPCRs are among the most important cell
surface receptors, with almost half of the drugs we utilize
exerting their action by modifying these receptors.
4 . lon channel-linked receptors ;
also referred to as ionotropic receptors, are responsible for
regulating the transduction of chemical signals across the cell
membrane in response to the chemical messenger (e.g.,
neurotransmitter) binding.
This class of receptor regulates the opening or closing of ion
channels that allow ions like Na+, K+, Ca2+, or Cl-, etc. to move
across the plasma membrane.
lon channels are pore-forming proteins also referred to as cell-
membrane bound receptors.
Ions pass down their electrochemical gradient through ion channels
without requiring ATP or metabolic energy.
Ion channels are mostly found on synaptic structures which are
primarily (but not exclusively) involved in neuronal activities.
Ion channels are, therefore, an important component of the
nervous system because they mediate conduction across nerve
synapses when activated by neurotransmitters.
lon channels also play a vital role in exerting cellular response to
toxins and venoms. Various biological processes involving fast
changes in cells such as the contraction of cardiac, skeletal, and
smooth muscles, activation of T-cells, and the release of hormones
are also mediated through ion channels.
functions of cell surface receptors ;
most ligands responsible for cell-cell signaling (including
neurotransmitters, peptide hormones, and growth factors) bind to
receptors on the surface of their target cells.
a major challenge in understanding cell-cell signaling is unraveling
the mechanisms by which cell surface receptors transmit the signals
initiated by ligand binding.
some neurotransmitter receptors are ligand-gated ion channels that
directly control ion flux across the plasma membrane.
Other cell surface receptors, including the receptors for peptide
hormones and growth factors, act instead by regulating the activity
of intracellular proteins.
These proteins then transmit signals from the receptor to a series of
additional intracellular targets, frequently including transcription
factors.
Ligand binding to a receptor on the surface of the cell thus initiates
a chain of intracellular reactions, ultimately reaching the target cell
nucleus and resulting in programmed changes in gene expression.
It regulates cell binding
It helps in signal transduction
It controls the membrane channels
It is also involved in immune responses and immunotherapy
It induces cell metabolisms, including cell growth, cell division
and cell death
Cell Receptor Based On Function ; Based on the function of the
receptors, scientists have divided them into mainly four categories. They
are based on function. They have not divided by the location of the
receptors. Based on the function, the four categories are:
1.Ligand-Gated Ion Channels: These are the receptors when they bind
with ligands they provide a channel to exchange the ion.
2.G-Protein Coupled Receptors: These are the receptors that are
activated when a ligand bind with the G-Protein. After that, it performs
certain operations.
3.Catalytic Receptors: These are the receptors that are responsible for
the enzyme secretion or the secretion of different substances from the
cell.
4. Nuclear Receptors: These are the receptors which are work with the
nucleus & help to develop the DNA.
functions ;
1. For Growth Of A Cell: Cell receptors act as the tool that helps to
make the growth of the cell. Whenever there is a need to have self-
growth, the cells secrete a special chemical. That chemical gets
attached to the receptors. This provides a signal to make a growth of
the cells by division.
2. In Immune System: Cell Receptors help to recognize the potential
threat to the human body. Immune cells secrete chemicals to
identify foreign substances. The chemical gets attached to the
foreign elements. After getting bind with it, it starts sending a proper
signal to the T Lymphocytes. Then T Cells recognize that foreign
element & destroy it.
3. For Hormonal Secretion: Hormones are a necessary element of the
human body. But one gland can’t able to secrete all the hormones
for the human body. Different glands secrete hormones for the
development of the body. The hormonal secretion is completely
executed with the help of cell receptors. Hormones act on specific
substances. This also works with the help of cell receptors. The
hormonal chemical gets attached to the specific cell & starts acting
upon it.
4. For Enzyme Secretion: As well as hormones, enzymes also act using
the cell receptors. Enzymes are chemicals. They act upon certain
substances. These enzymes bind with the cell receptors of that
substances. And helps to decompose it to any further other
substance. In this way, it is clear that cell receptors also help in
human digestion in a large context.
5. Other Functions: Along with the above functions, there are several
functions of the cell receptors. They are responsible for the death of
any cell. When a cell seems a threat to the body, it secretes the
proper signal to destroy itself. Also, there are a lot of functions are
executed by cell receptors. Simply, they are responsible for each
communication between the cells.
