Intercellular Communication & Signal Transduction Mechanism

Department of Physiology School of Medicine University of Sumatera Utara

Intercellular Communication and Signal Transduction

The ability of cells to communicate with each other is essential for coordination of their diverse activities to maintain homeostasis as well as to control growth and development of the body as a whole

Intercellular Communication and Signal Transduction

These signals come from distant cells (known as endocrine signals, like hormones and growth factors); they come from neighboring cells (known as paracrine signals); they even come from within the same cell (known as autocrine signals)

Signaling Types
Local signaling
Gap junction Paracrine--signaling that affects neighboring cells Autocrine--secretion that affects same cell

Long Distance
Endocrine--secretion of a substance that is released

into the blood and affects a distant target

Gap Junction
A gap junction or nexus is a junction between certain cell-types that allows different molecules and ions to pass freely between cells. The junction connects the cytoplasm of cells. One gap junction is composed of two connexons (or hemichannels) which connect across the intercellular space.

Gap Junction
At gap junctions, the intercellular spaces narrows from 2nm to 3nm and unit connexons in the membrane of each cell are lined up with one another

Gap Junction
Allows for chemical communication between cells, through the transmission of small second messengers, such as Ca++, although different connexin subunits can make selectivity for particular small molecules. Generally allows molecules smaller than 1,000 Daltons to pass through,

Gap junctions are particularly important in the cardiac muscle: the signal to contract is passed efficiently through the gap junctions, allowing the heart muscle cells to contract in tandem.

Paracrine
The signal chemical is called the paracrine agent. They are secreted into the interstitial fluid and diffuse to adjacent cells, where they have their biologic action

Paracrine

Autocrine
Autocrine is a form of hormonal signalling in which a cell secretes a hormone, or chemical messenger (called the autocrine agent) that binds to autocrine receptors on the same cell, leading to changes in the cell

Autocrine

The endocrine system

The other communication system in the body is made up of endocrine glands that produce hormones, chemical substances released into the bloodstream to guide such processes as metabolism, growth, etc.

The endocrine system

The endocrine system is an information signaling system much like the nervous system. However, the nervous system uses nerves to conduct information, whereas the endocrine system uses blood vessels as information channels

The endocrine system

Glands located in many regions of the body release into the bloodstream specific chemical messengers called hormones, which regulate the many and varied functions of an organism.

The endocrine system

The typical endocrine organ is a ductless gland that secretes chemical mediators directly into local blood vessels which circulate within the body via the bloodstream. These hormones travel to distant organs to regulate the target organ's function.

The endocrine system

Major endocrine glands. (Male left, Female on the right.)
1. 2. 3. 4. 5. 6. Pineal gland Pituitary galnd Thyroid galnd Thymus Adrenal gland Pancreas

7.
8.

Ovary
Testes

The endocrine system

Intercellular Communication and Signal Transduction

Gap junctions Message transmission Local or general Specificity depends on Directly from cell to cell Local Anatomic location Synaptic Across synaptic cleft Local Anatomic location & receptors Paracrine & Autocrine
By diffusion in interstitial fluid

Endocrine By circulating body fluids General Receptors

Locally diffused Receptors

Signal Transduction in Cells

Cells in our body are surrounded by a lipid membrane. The "water-loving" heads of the phospholipid molecules (blue) are directed towards the outer and inner surfaces of the membrane. Many proteins stretch through the entire membrane.

Signal Transduction in Cells

Extracellular signaling molecules (usually hormones, neurotransmitters, cytokines, growth factors or cell recognition molecules) attach to the receptor, triggering changes in the function of the cell The binding initiates a chemical change on the intracellular side of the membrane

Signal Transduction in Cells

Extracellular signal molecule: an extracellular signal molecule is produced by one cell and is capable of traveling to neighboring cells, or to cells that may be far away. Receptor protein: the cells in an organism must have cell surface receptor proteins that bind to the signal molecule and communicate its presence inward into the cell.

Intracellular signaling proteins: these distribute the signal to the appropriate parts of the cell. The binding of the signal molecule to the receptor protein will activate intracellular signaling proteins that initiate a signaling cascade (a series of intracellular signaling molecules that act sequentially).
Target proteins: the conformations or other properties of the target proteins are altered when a signaling pathway is active and changes the behavior of the cell

Signal Transduction in Cells

A first messenger (1), a molecule of adrenaline, binds to a specific adrenaline receptor (2), a discriminator. Thereby, the transducer (3), a G protein - composed of alpha-, beta- and gamma subunits - is activated, This, in turn, stimulates the amplifier (4), adenylate cyclase, which produces (5) the second messenger, cyclic AMP, from (6) ATP (adenosine- triphosphate). (7) A cascade of enzymatic reactions alters the behaviour of the cell and (8) via phosphorylation (9) glycogen is transformed to (10) glucose, which the cell uses to generate ATP. Phosphorylation can also alter membrane proteins, for example, ion channels (11)

Signal Transduction in Cells

Activation and Inactivation of the G Protein

1. The G protein, composed of alpha-, beta- and gamma-subunits, in its resting state with bound GDP

Signal Transduction in Cells

Activation and Inactivation of the G Protein

2. The receptor with bound hormone activates the G protein and replaces GDP...

Signal Transduction in Cells

Activation and Inactivation of the G Protein

3. ...with GTP and the G proteins is activated. The subunits separate.

Signal Transduction in Cells

Activation and Inactivation of the G Protein

4. Some seconds later the GTP, bound to the alpha-subunit, is hydrolysed to GDP. The subunits recombine.

Membrane receptors
specialized integral membrane proteins that take part in communication between the cell and the outside world

play a unique and important role in cellular communications and signal transduction

Membrane receptors
Membrane receptors generally function by binding the signal, or ligand and causing the production of a second signal (second messenger) that causes a cellular response. The diagram shows how the receptor for insulin functions.

Membrane receptors

A pair of insulin molecules bind to receptors, causing a change in the protein structure that exposes a kinase or phosphate transferring enzyme inside the cell The activated receptor kinase transfers a phosphate group to adjacent receptor molecules, leading to the activation of subcellular proteins and a cellular response to insulin The receptors must be integral membrane proteins that pass through the lipid bilayer. Through this system, an insulin molecule can cause a response inside the cell without passing through the lipid bilayer

Cellular response