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MDC Researchers Link Protein Tether to Touch Perception — Tiny Protein Filament Opens and Closes Ion Channels

Humans and animals are able to perceive even the slightest vibration and touch of the skin. Mechanosensitive ion channels play a crucial role in the mediation of these sensations. Ion channels are pores in the cell membrane which are highly responsive to external signals. Mechanosensitive ion channels open at the slightest vibration and allow ions (electrically charged particles), to cross the cell membrane, which causes an electrical current until the channel closes again. Until now it was unclear how the ion channels were opened. Dr. Jing Hu and Professor Gary Lewin of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now discovered the presence of a protein filament that causes the ion channels to open and shut like a tethered gate (EMBO Journal,Vol. 29, No. 4, pp 855 – 867; doi: 10.1038/emboj.2009.398)*.

In their
study, the researchers showed that the opening and closing of ion channels literally
hangs by a thread”. This protein thread or filament, as Dr. Hu and Professor
Lewin demonstrated, is synthesized by the mechanosensitive endings of cutaneous
neurons and is probably an integral part of the mechanosensitive mechanism.

The thread
is firmly tethered in the extracellular matrix (ECM), the connective protein
glue” that helps to hold cells together. However, the filament is located so
close to the mechanosensitive ion channels that it can probably directly open
them. The filaments were found to be 100 nanometers (nm) long (1 nanometer is
equivalent to one billionth of a meter) and may link the ion channels of the
cell membrane to the ECM at mechanosensitive sensory endings of the skin in
mice.

The
researchers demonstrated both with neuronal cultures and experiments using the
isolated skin with receptors attached that the opening of mechanosensitive ion
channels upon slight touch requires the 100nm protein filament. The stretching
of sensory membranes by small mechanical stimuli does not appear to play any
significant role in touch receptors.

When the
researchers cleaved the filament with specific enzymes, thus cutting the link
between the sensory ending and the extracellular matrix (ECM), the neurons were
rendered completely insensitive to mechanical stimulation and touch. However,
if the researchers waited twelve hours the filaments were again synthesized by
the sensory cells and they became mechanosensitive once more.

This
means that touch can be perceived only when the protein filament is present. The
filament renders the mechanosensitive ion channel highly sensitive to force and
may even directly participate in opening and closing the channel ” Professor
Lewin explained.

However,
this does not apply to the perception of mechanical pain. Pain receptors” he
emphasized, are not dependent on this filament.” According to the neurobiologists, the protein
filaments may in the future be of great interest to medical research.
Advancements in this area could help people whose sense of touch is impaired due
to old age, improving their general well-being and mobility. There are also
common syndromes where there is oversensitivity to touch, in the case of
neuropathic pain where the slightest touch of 
feather may be perceived as painful, again accessing the tether may help
in alleviating the symptoms.

*Evidence for a protein tether involved in somatic touch

Jing Hu1,2,4, Li-Yang Chiang1,2, Manuel Koch3 and Gary R. Lewin1

1Department of Neuroscience, Max-Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Robert-Rössle-Str. 10, Berlin-Buch D‑13125 Germany. 3Center for Biochemistry, Department of Dermatology, and Center for Molecular Medicine Cologne, Medical Faculty, University of Cologne, D‑50931, Cologne, Germany.

2These authors made an equal contribution.

4Present address

Center for Integrative Neuroscience (CIN), Paul-Ehrlich-Str. 15 – 17, 72076 Tübingen,Germany

Barbara
Bachtler
Press
and Public Affairs
MaxDelbrück
Center for Molecular Medicine (MDC)
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10; 13125 Berlin; Germany
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+49 (0) 30 94 06 — 38 96
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