A Protein Essential For Touch Sensation - First Evidence For A Touch Receptor Ge

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A Protein Essential For Touch Sensation - First Evidence For A Touch

Receptor Gene In Mammals

http://www.medicalnewstoday.com/medicalnews.php?newsid=59288 & nfid=nl

The skin is the largest sensory organ in humans. The sensory

innervation of the skin allows us to perceive touch and pain. Now,

Christiane Wetzel, a researcher in the laboratory of Professor

Lewin at the Max Delbrück Center for Molecular Medicine (MDC) Berlin-

Buch, Germany, and her colleagues have deciphered the function of a

molecule necessary for the conversion of mechanical stimuli into

neural impulses. They have demonstrated that this molecule, a

protein called SLP3, is essential for the detection and

discrimination of fine tactile stimuli. This study provides the

first evidence for a touch receptor gene in mammals and shows that

molecules may in the future prove to be important therapeutic

targets for the control of chronic pain. The findings of Christiane

Wetzel and Professor Lewin were published in Nature online (DOI:

10.1038/nature05394).

Christiane Wetzel could show that mice lacking SLP3 are unable to

distinguish normally between finely structured surfaces. This

serious sensory deficit could be traced to the fact that around one

third of the mechanoreceptors in the skin of SLP3 mutant mice fail

to respond to any mechanical stimulation.

Although the sensation of touch is not usually associated with pain

this situation is dramatically altered after injury to nerve. Thus

many people with such injuries suffer from chronic pain in which

even light brush stimuli can provoke intense pain.

This type of pain, called neuropathic pain, can be modelled in

animals and mice lacking SLP3 show virtually no touch-evoked pain

when confronted with such a lesion. This data further indicates that

by targeting molecules involved in the detection of touch one could

achieve a novel way to control neuropathic pain a clinical condition

for which few effective treatment options are available.

Touch and pain are detected by sensory neurons which are located in

the dorsal root ganglia (DRG) and their " working end " is in the skin

attached to the cell body by a long process called the axon.

Mechanical stimuli of the skin (brush or pressure) activates

the " working end " of the sensory receptor and initiates an

electrical signal that is relayed to the spinal cord and brain.

The sensory receptor must then convert a mechanical signal into an

electrical signal and this process is called sensory

mechanotransduction. It is this process of sensory

mechanotransduction, that is very poorly understood in mammals. It

is thought that mechanical stimuli are converted into electrical

events by specialized ion channels, these channels can be opened

when the membrane is physically indented, leading to an increased

flow of charged ions into the cell to produce an electrical signal.

In this study the activity of such ion channels was measured in

response to extremely small indentation stimuli (nanometer range).

It was found that in many sensory neurons SLP3 was required for the

function of such mechanosensitive channels.

This study is the very first to show any protein that is directly

involved in the detection of touch in mammals. Many genes have been

shown to be necessary for mechanosensation in simpler organisms like

worms and flies. The SLP3 protein is also very closely related to

such a necessary mechanotransduction protein in worms called MEC-2.

This study therefore provides the first evidence for a touch

receptor gene in mammals and shows that molecules may in the future

prove to be important therapeutic targets for the control of chronic

pain.

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*A stomatin-domain protein essential for touch sensation in the

mouse

Christiane Wetzel1, Jing Hu1,5, Dieter Riethmacher2,5, Anne

Benckendorff1,5, Lena Harder1, s Eilers1, Rabih Moshourab1,

ey Kozlenkov1, Dominika Labuz3,Ombretta Caspani3, Bettina

Erdmann4, Halina Machelska3, A. Heppenstall1,3, and R.

Lewin1

1 Growth Factors and Regeneration Group, Max-Delbrück Center for

Molecular Medicine and Charité Universitätsmedizin Berlin, -

Rössle-Str. 10, Berlin-Buch D-13125 Germany.

2 Zentrum für Molekulare Neurobiologie, Universität Hamburg,

Falkenried 94, 20251 Hamburg, Germany.

3 Klinik für Anaesthesiologie und Operative Intensivmedizin, Charité

Universitätsmedizin Berlin, Campus lin,Hindenburgdamm

30, D-12200 Berlin, Germany.

4 Electronmicroscopy, Max-DelbrückCenter for Molecular Medicine,

-Rössle-Str. 10, Berlin-Buch D-13125 Germany.

5 These authors made an equal contribution.