No. 40/December 15, 2006

MDC Researchers: A Protein Essential for Touch Sensation - First Evidence for a Touch Receptor Gene in Mammals

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 Gary 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.

 

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

Christiane Wetzel1, Jing Hu1,5, Dieter Riethmacher2,5, Anne Benckendorff1,5, Lena Harder1, Andreas Eilers1, Rabih Moshourab1, Alexey Kozlenkov1, Dominika Labuz3,Ombretta Caspani3, Bettina Erdmann4, Halina Machelska3, Paul A. Heppenstall1,3, and Gary R. Lewin1

1Growth Factors and Regeneration Group, Max-Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Robert-Rössle-Str. 10, Berlin-Buch D-13125 Germany. 2Zentrum für Molekulare Neurobiologie, Universität Hamburg, Falkenried 94, 20251 Hamburg, Germany. 3Klinik für Anaesthesiologie und Operative Intensivmedizin, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany. 4Electronmicroscopy, Max-DelbrückCenter for Molecular Medicine, Robert-Rössle-Str. 10, Berlin-Buch D-13125 Germany. 5These authors made an equal contribution.

 

Barbara Bachtler

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