This document summarizes cell signaling and the different types of extracellular signaling. It describes the key steps in extracellular signaling which involve synthesis and release of signaling molecules, transport to target cells, binding of signals to receptors, and signal transduction. Extracellular signaling can be classified as endocrine, paracrine, autocrine, or juxtacrine depending on the location of signal production and target cells. Receptor proteins play an important role in transmitting signals to cells and are classified as G protein-coupled receptors, ion channel receptors, or enzyme-linked receptors.

1. CELL SIGNALING
BY KANCHAN YADAV
MSc Agril. Biotechnology
RPCAU, Pusa, Bihar

2. Introduction
• All cells receive and respond to
signals from their surroundings
.
• Variety of signal molecules that
are secreted or expressed on
the surface of one cell and bind
to receptors expressed by other
cells

3. Extracellular signaling involves following steps :
Synthesis and release of the signaling molecule by the signaling cell
Transport of the signal to the target cell
Binding of the signal by a specific receptor leading to its activation
Initiation of signal transduction pathways

4. Extracellular signaling by signal molecules can
be classified into four categories
• Endocrine signaling
• Paracrine signaling
• Autocrine signaling
• Juxtacrine signaling

5. Endocrine signaling
• Signaling molecules act on target cells distantly located from their site of
synthesis
• It is a long range signaling
• Signal molecule transported by the blood stream

6. Paracrine signaling
• Signaling molecules released by a
cell affect target cells only in close
proximity
• For eg. Action of neurotransmitters
in carrying signals between nerve
cells at a synapse

7. Autocrine signaling
• Signaling molecules produce an effect on same cell that produces it
• For eg. Response of cells of the vertebrate immune system to foreign
antigens

8. Juxtacrine signaling
• Signal molecules do not diffuse from the cell producing it and cell bearing
signal molecules interact with receptor proteins of adjacent responding cells.
• Requires physical contact between the cells involved

9. Signal molecules
Signal molecules are chemically heterogenous compounds
Two categories : membrane bound and secretory signal molecules
ENDOCRINE
SIGNAL
MOLECULES
PARACRINE
SIGNAL
MOLECULES
AUTOCRINE
SIGNAL
MOLECULES

10. RECEPTOR MOLECULE
• Cellular response to a particular extracellular signal molecule depends on its binding
to a specific receptor located on the surface of a target cell or in its nucleus or
cytosol.
• Receptors are chemically protein or glycoprotein molecules which bind to signaling
molecules(termed ligands)
• Binding of a ligand to its receptor causes a conformational change in the receptor
that initiates a sequence of reactions leading to a specific cellular response
• Based on location, receptors are classified into two broad categories- intracellular
receptors and cell surface receptors.

11. Cell surface receptors
• All hydrophilic signaling mlecules as well as some lipophilic molecules ,bind
to the cell surface receptor proteins
• These act as signal transducers to produce intracellular messengers
• These messengers stimulate the sensors and effectors responsible for
activating cellular responses

12. • Most cell surface receptor proteins belong to one of the three classes:
1. G Protein Coupled Receptors (GPCRs)
2. Ion channel receptors
3. Enzyme linked receptors

13. GPCR and G PROTEIN
• GPCRs are the largest family of cell surface receptors
• Transmit signals to intracellular targets via the intermediary action of
guanine nucleotide binding protein called G proteins.
• GPCRs are present in all eukaryotes

14. GPCR adaptation
• Adaptation is defined as the diminution of receptor signaling in the presence
of continued or repeated stimulation
• Target cells usually use two processes to adapt, when they are exposed to a
high concentration of signal molecules for prolonged periods :
• Desensitization
• Internalization

15. Desensitization
• It is described as the loss of response to
prolonged or repeated stimulation
• It starts with a phosphorylation of several
Ser and Thr residues in the cytoplasmic
domains of the receptor by G Protein
coupled receptor Kinase(GRKs)
• GRK- phosphorylated receptors then binds
with arrestin protein and uncouple the
receptor and G Protein

16. Internalization
• It involves removal of receptors from the cell surface
• Internalized receptors may be either re exposed through exocytosis or
degraded in lysosomes
• Internalisation of cell surface receptors to intracellular membranous
compartments is termed receptor sequestration
• Destruction of receptors in lysosomes after internalization is termed
receptor down regulation

17. Ion channel linked receptors
• Also known as transmitter gated ion channels or ionotropic receptors
• They are involved in rapid synaptic signaling between electrically excitable
cells
• Mediated by a small number of neurotransmitters that transiently open or
close an ion channel formed by the protein to which they bind
• Hence changing the ion permeability of the plasma membrane and thereby
the excitability of the postsynaptic cell

18. ENZYME LINKED RECEPTORS
• Second major type of cell surface receptor
• Their cytosolic domain either has as intrinsic enzyme activity or associates
directly with an enzyme

19. Two component signaling systems
• Most common form of signaling pathway that responds to extracellular
events in bacteria and plants
• Consists of a sensor that is an autophosphorylating histidine kinase and a
response regulator,which transfers the phosphate from sensor kinase to a
conserved aspartate within itself
• Usual end target is regulation of gene
transcription

20. Quorum sensing
• Bacterial communication phenomenon
• It allows bacteria to communicate using secreted signal molecules to assess their population
density
• It enables a population of bacteria to collectively regulate gene expression
• It detect the concentration of a particular signal molecule termed autoinducer which is correlated
with cell density
• As the bacterial population grows,the concentration of autoinducer in the surroundings increases
• Both gram positive and gram negative bacteria use quorum sensing communication circuits to
regulate physiological activities including symbiosis,virulence,competence,conjugation,antibiotic
production, motility and sporulation