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Cellular communication and co-operation

The world is dominated by single-celled organisms. Whether one is talking about total biomass or number of unique species, single celled organisms rule.

The world is dominated by single-celled organisms. Whether one is talking about total biomass or number of unique species, single celled organisms rule.

This is not necessarily obvious as most of the living organisms that we encounter tend to be large and multicellular. Trees, people, dogs, and most things that you can see are multicellular and it biases us into thinking that most of life is the same way.

But the 100,000 or so bacteria that are living on each square centimetre of your skin would beg to differ. They and their cousins are everywhere - they are just hard to see.

Stephen Jay Gould once argued, in one of his science columns, that despite the fact that there are nearly one million species of multicellular organisms named (and 80% of those are arthropods), there are a great many more that are not multicellular. We live in the "Age of Bacteria" and always have.

So why is it so hard to exist as a multicellular organism? Why are there so few?

The answer is that for cells to coagulate into a multicellular creature, they must learn to both communicate and cooperate. This is not an easy thing to do.

Early work on the cell showed that each cell in the body is surrounded by a lipid bilayer membrane. The lipids are molecules with a water loving head or polar group and a fat loving tail. They line up in two rows (a bilayer) with the head groups pointing out into the surrounding water and the tails pointing inward at each other.

Communication requires that a signal must transfer across this membrane boundary - either an electrical signal from a nerve or a chemical signal. However, fatty acids or lipids are not particularly good at conducting electricity or at allowing the passage of charged ions or molecules.

The fact that nerve conduction wasn't involved in cell communication was reinforced by early studies of adrenalin's effects on the body. Giving a patient or a laboratory animal adrenalin results in diverse responses - for example, the heart rate increases, the bronchial tubes dilate, blood vessels constrict, the pupils dilate, and the intestinal tract shuts down.

In physiological terms, adrenalin produces a total of nine different responses in the body with some being to excite specific cells while other responses inhibit other cells.

When scientists paralyzed the nervous system of lab animals, they found that they would still respond to adrenalin in exactly the same way. The nervous system is not the route of cellular communication.

Rather, there has to be a receptor built into the cell membranes of the different organs that responds specifically to the hormone involved. But finding the receptor was a long and convoluted search.

In the 1940s, an American scientist, Raymond Ahlquist, was able to show that there must be at least two different types of receptors for adrenalin with one affecting the smooth muscle cells controlling blood vessels and the other involved in stimulating the heart.

He labeled the receptors "alpha" and "beta". It wasn't long after that the first beta-blockers were synthesized and used to treat chronic high blood pressure. How these drugs worked remained a bit of a mystery and after a couple of decades, Ahlquist began to lose hope in finding them.

Enter one of this year's Nobel Laureates in Chemistry, Robert Lefkowitz. In the late 1960s, he started his research into identifying receptor sites. He was able to synthesize hormones with radioactive iodine attached and by following the radioactivity, he was able isolate the receptors of the cell surfaces.

Furthermore, he was able to show that the interaction of the hormone with the receptor on the cell's surface triggered a process inside the cell. Other researchers were able to identify what was happening inside the cell. A signal from the receptor activated a G-protein and this, in turn, triggers a number of reactions that alter the metabolism of the cell. Consequently, the receptors are called "G-Protein Coupled Receptors" (GPCRs).

In the 1980s, Lefkowitz hired a young doctor by the name of Brian Koblika, the other recipient of this year's Nobel Prize in Chemistry. Kobilka was interested in the adrenergic receptors from his experience in emergency medicine where a shot of epinephrine could mean the difference between life and death.

Over the years, he was able to determine the exact structure of the GPCRs. Indeed, his latest work has captured a GPCR right in the middle of reacting with both the hormone trigger and the G-protein complex engaged.

More importantly, the number of cellular processes that have been identified to depend on GPCRs has increased significantly. Everything from sight to smell to taste to our hormones depend upon cellular communication and cooperation through these receptor sites.

Being a multicellular organism requires cells to talk.

Receptors make it happen.