SIGNALING MOLECULES

SWATI BAYYANA M.Sc. LIFE SCIENCES

CELL AND ENVIRONMENT INTERACTIONAll cells are able to sense and respond to

substances present in their external environments. 

The ability to respond to external stimuli enhances a cell's chance of survival, especially in multicellular organisms.

Chemicals that could pass into cells, and bind directly to proteins inside the cell and modulate their activities.

In E. coli cells, the uptake of arabinose from the environment triggers the production of enzymes necessary for its utilization.

SIGNALLING MOLECULES

Signaling molecules are the molecules that are responsible for transmitting information between cells in your body.

Most of them have been highly conserved in evolution.

Different types of cells respond differently to same signal molecules

EXTRACELLULAR SIGNAL MOLECULES

 Extracellular signaling molecules are critical regulators of physiology and development in organisms.

 There are many different types of signals, including, peptides, small lipophilic molecules, small hydrophilic molecules and gases.

Binding of extracellular signaling molecules to cell-surface receptors trigger intracellular pathways that ultimately modulate cellular metabolism, function, or development.

SIGNALLING PATHWAYSIn animals, signaling by extracellular, secreted

molecules can be classified into three types — endocrine, paracrine, or autocrine — based on the distance over which the signal acts.

In endocrine signaling, signaling molecules, called hormones, act on target cells distant from their site of synthesis by cells of endocrine organs. 

In paracrine signaling, the signaling molecules released by a cell only affect target cells in close proximity to it.

In autocrine signaling, cells respond to substances that they themselves release.

PEPTIDE HORMONES

◦ These are water soluble molecules◦ They all bind to cell surface receptors◦ Such as insulin, growth factors, and glucagon, etc.

STEROID HORMONES

◦ They are lipid soluble molecules◦ Interact with receptors in the cytosol or 

nucleus. ◦ For example, estrogen and progesterone.

PROSTAGLANDINS

◦ Prostaglandins are lipid autacoids derived from arachidonic acid.

◦ Prostaglandins play a key role in the generation of the inflammatory response.

◦ They act as autocrine or paracrine factors .

NITRIC OXIDE

◦ NO diffuses freely across cell membranes.◦ It is quickly consumed close to where it is

synthesized.◦ Thus NO acts in a paracrine or even autocrine fashion

Nobel Prize in Physiology or Medicine in1998 to Robert F Furchgott, Louis J Ignarro and Ferid Murad for their discoveries concerning "the nitric oxide as a signalling molecule in the cardiovascular system"

INTRACELLULAR SIGNAL MOLECULES

Intracellular signaling molecules relays signals received at receptors, ultimately results in signaling cascade.

It transduce and integrate signals before relaying a signal forward.

Intracellular signaling complexes enhance the speed, efficiency and specificity of the response.

A combination of small and large intracellular signaling molecules relays signals

The small intracellular signaling molecules, called as small intracellular mediators or second messengers. Examples – cAMP , Ca+2, etc.

cAMP - It is non-specific and can generate a variety of responses in the cell.

Ca++ effects includes exocytosis of secretory vesicles, muscle contraction or the inducement of mitosis in fertilized eggs.

cAMP is synthesized by an integral membrane protein, adenylyl cyclase, using ATP as a substrate.

A large conformational change in the protein upon Ca+2 binding.

Many intracellular signaling molecules function as Molecular SwitchesG proteins (GTPase switch

proteins) - Signal results in the release of GDP and the

binding of abundant GTP. After a short period of time they hydrolyse GTP and come back to their “off” state.

Protein Kinases - They add phosphate groups to themselves and/or other proteins at either serine/threonine, or at tyrosine residues. Their activity can be regulated by second messengers, interaction with other proteins, or by phosphorylation itself..

REGULATIONFeedback loops are of great importance as

they regulate many chemical and physical processes in cells.

A positive feedback loop can transform the behavior of the responding cells.

A negative feedback loop counteracts the effect of a stimulus, limits the level of response.

When Cell Communication Goes Wrong

 Following are just a few ways in which cell communication can go wrong, resulting in disease.◦Losing the signal- In type I

diabetes, the pancreatic cells that produce insulin are lost. 

◦Signal doesn’t reach its target- Multiple sclerosis is a disease in which the protective wrappings around nerve cells in the brain and spinal cord are destroyed.

◦Multiple breakdowns- The result is uncontrolled cell growth, often leading to cancer

Recent advancements….. RNA can act as an extracellular signal

is emerging. Studies in plants first showed that the phenomenon of co-suppression in response to transgene expression is mediated by RNA signaling.

Hydrogen peroxide and Nitric oxide functions as signaling molecules in plants.

REFERENCESLodish –Molecular biology of cell

Albert- Molecular biology of cell

Lehninger –Principles of biochemistry

Stephen Neill; Hydrogen peroxide and Nitric oxide as signaling molecules in plants; Journal of Experimental Biology; December 2001; vol 53.

http://www.nature.com/scitable/topicpage/cell-signaling-14047077

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CellSignaling.html

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