Cellular communication occurs through chemical signaling via ligands and receptors. There are several forms of cellular signaling including autocrine, paracrine, endocrine, synaptic, and cell-cell contact signaling. Ligands can be small hydrophobic molecules that pass through the cell membrane or bind to extracellular domains of cell surface receptors. Receptors can be intracellular or cell surface receptors. Common types of receptors include G-protein coupled receptors, receptor tyrosine kinases, and ion channel receptors. Binding of ligands to receptors triggers downstream signaling pathways involving second messengers like cAMP, cGMP, calcium ions, and inositol phosphates to produce a cellular response.

1. By-Gouthaman PP

2. INTRODUCTION
 Cellular communication takes place via chemical signals
 Which are usually biomolecules such as proteins
 For communication to take place recipient cell is to have receptors,
and the recipient is called Target cell
 The binding of receptor and signal molecule triggers a change within
the cell by alteration of receptor molecule
 The signaling molecules thus are termed as Ligands
 The signals carried by ligands can lead to changes leading from
activity of specific genes to regulation of entire processes

3. CELLS RESPOND TO

4. FORMS OF SIGNALING
 AUTOCRINE, Transmission in same cell.
 PARACRINE, Nearby cells or short distance
 ENDOCRINE, Transduction to long distances through circulatory
system.
 SYNAPTIC, Transmission of Signals between nerve cells
 CELL-CELL CONTACT, Signaling through channels called Gap J
unctions

6. LIGANDS AND RECEPTORS
 Signaling takes place Via the Ligand-Receptor Interaction
 Ligands and Receptors in closely matched pairs, they show
specificity
 Binding of Ligand to Receptor changes its activity thus
signaling for change inside the cell

7.  Ligands are of two types:
1) Ligands that can enter the cell- Small hydrophobic ligands can
pass through the plasma membrane and bind to the receptors in
nucleus or the cytoplasm. (e.g.: Steroid hormones such as estradiol,
testosterone, Nitric Oxide)
2) Ligands that can bind on the outside of the cell- Water soluble
ligands are polar or charged and cannot readily cross the plasma
membrane. They bind to the extracellular domains of cell surface
receptors which induces the action of secondary messengers. (e.g.:
Peptide ligands and hydrophilic organic molecules)

8.  Similarly there are two types of receptors:
1) Intracellular receptors- They are found in the inside of the cell,
typically in cytoplasm or the nucleus.(e.g.: Receptors for the hormones
Estrogen and Testosterone)
2) Cell surface receptors- These are membrane anchored proteins
that binds to the ligands on the outside surface of the cell. A typical cell
surface receptor contains an extracellular ligand binding domain, A
hydrophobic domain extending through the cytoplasm and an
intracellular domain.(e.g.:G-protien coupled receptors, receptor tyrosine
kinase etc.)

11. G- PROTEIN COUPLED RECEPTORS
 G-protein attached to the cytoplasm side of plasma membrane
function as a molecular switch.
 60% of medicines function by interacting with G-proteins.
 Binary switching mechanism.
 All G-protein coupled receptors(GPCRS) contain seven membrane
-spanning regions.
 The GPCR family includes receptors for numerous hormones and
neurotransmitters, light activated receptors (Rhodopsin) in the
eye, odorant receptors in the mammalian nose etc.
 Contain α, β, γ subunit. Hetero trimeric protein.
 Humans have 1000 diff. GPCR. Each with specific signals.

12. TRANSMEMBRANE RECEPTORS

16.  Enzyme linked cell surface receptors found in humans as well
as other animals
 It transfers phosphate to the amino acid Tyrosine
 The ligand first binds to the extracellular domain of the two
nearby RTK.
 This results in dimerization of the neighboring RTK’s
 The receptors then Phosphorylates the Tyrosine domain and it
transmits signal to other molecules in the cell
 The phosphorylated receptors acts as docking platform for other
protein’s
 This initiates a downstream signaling cascade that leads to
cellular response
TYROSINE KINASE RECEPTORS

18. ION CHANNEL RECEPTORS
 Ion channels that open in response to the binding of a ligand
 The receptor has a membrane spanning region with a hydrophilic
channel through the middle of it
 Ions of a particular type are able to pass through when the confor
mation of the protein changes due to the binding of ligand
 In another case when the ligand binds, the channel may close
 Changes in ion level influences ion binding enzyme and voltage
sensitive channels

20. JAK-STAT PATHWAY
 Transmits information from extracellular chemical signals to the
nucleus
 Results in the transcription and expression of genes involved in
immunity, proliferation, differentiation, apoptosis and oncogenesis
 3 main components: A cell surface receptor, Janus kinase(JAK) and
two signal transducer and activator of transcription(STAT) protiens
 Defects results in immune deficiency syndromes and cancers

22.  Intracellular signal molecules which trigger transduction cascade
 Many pathways involve second messengers (small messengers,
non protein molecules) that pass along a signal initiated by the
binding of a ligand to its receptors
 First discovered Secondary messengers are cAMPs.
 Examples are cAMP, cGMP, Calcium ions, Inositol phosphates
etc.
SECOND MESSENGERS

23. cAMP PATHWAY

26. INOSITOL PHOSPHATES
 Phospholipids called phosphatidylinositol can be phosphorylated
and snipped in half
 The resulting two fragments, both acts as second messengers
 Phosphatidylinositol 4,5-bisphosphate (PIP2) is cleaved by
phospholipase C
 The resulting fragments are diacylglycerol(DAG) and inositol
triphosphates(IP3)

28. THANK YOU