Understanding Schwann cell-neurone interactions: the key to Charcot-Marie-Tooth disease?
Charcot-Marie-Tooth disease (CMT) comprises a heterogeneous group of disorders. The most frequent subtype is caused by increased PMP22 gene dosage or missense point mutations affecting the PMP22 gene (CMT type 1A; CMT1A). Animal models in rat and mouse with the corresponding PMP22 alterations are available and mimic many aspects of the human diseases. Detailed examinations of the animal mutants, together with complementary data from patients, point towards altered Schwann cell-neurone interactions as a major underlying mechanism of CMT1A and related hereditary neuropathies. This is evident from the finding that mutated proteins affecting either Schwann cells or neurones have a profound influence on their partner cells. Recently, a number of novel genes causing various forms of CMT have been identified which are expressed either mainly by Schwann cells and/or by the accompanying neurones. These genes can be viewed, in analogy to classic experiments routinely performed in lower vertebrates, as the result of a 'functional screen' revealing crucial players in the interactions between Schwann cells and neurones. Studying how Schwann cell and axon-encoded proteins are functionally interconnected will be an exciting task for the future. It will not only yield insights into the molecular and cellular basis of neuropathies but also provide crucial information about the interplay between Schwann cells and neurones in general.
Maier
Marcel
M
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, Zurich.
Berger
Philipp
P
Suter
Ueli
U
D000818:Animals; D001369:Axons / Q000502:physiology; D002450:Cell Communication; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D006801:Humans; D023421:Models, Animal; D009185:Myelin Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology*
D009185:Myelin Proteins; C073687:PMP22 protein, human; C489545:Pmp22 protein, mouse; C489546:Pmp22 protein, rat