 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Electronic Letters to:
- Brief Communications:
Alessandro Nodari, Stefano C. Previtali, Gabriele Dati, Simona Occhi, Felipe A. Court, Cristina Colombelli, Desirée Zambroni, Giorgia Dina, Ubaldo Del Carro, Kevin P. Campbell, Angelo Quattrini, Lawrence Wrabetz, and M. Laura Feltri6β4 Integrin and Dystroglycan Cooperate to Stabilize the Myelin Sheath
J. Neurosci. 2008; 28: 6714-6719[Abstract] [Full text] [PDF]
eLetters: Submit a response to this article
Electronic letters published:
Myelin-related mutants identify high vulnerability of the near-nodal compartment of nerve fibers
- Rudolf Martini (27 June 2008)
Myelin-related mutants identify high vulnerability of the near-nodal compartment of nerve fibers 27 June 2008 
Rudolf Martini,
Professor of Neurobiology
Department of Neurology, University of Wuerzburg, Josef-Schneiderstr. 11, D-97080 WuerzburgSend letter to journal:
Re: Myelin-related mutants identify high vulnerability of the near-nodal compartment of nerve fibers
rudolf.martini{at}mail.uni-wuerzburg.de Rudolf Martini
Nodari and colleagues impressively demonstrated in their recent paper (Nodari et al., 2008) that Schwann-cell-specific deficiency of beta4 integrin does not impair myelin generation per se, as initially shown by others, but leads to the formation of myelin infoldings near the nodes of Ranvier. Other features are the disorganization of potassium channels and abnormal electrophysiological features. When combined with an additional lack of another laminin receptor, dystroglycan, the phenotype is aggravated and accelerated. A numerical increase of phagocytosing macrophages is indicative of the pathogenetic involvement of these cells.
The findings by Nodari and colleagues add to previous evidence for the high vulnerability of the near-nodal compartment of larger caliber fibers initially described for heterozygous MPZ null mutants (Martini et al., 1995). Interestingly, in both MPZ and beta4 integrin mutants, a late-onset degenerative phenotype implicating macrophages is observed (Carenini et al., 2001; Nodari et al., 2008). The disorganization of the presumably juxtaparanodal structures in myelin-related mutants, but also in aging wild-type rodents, might be a pathological consequence of a labile, molecularly specialized structure that not only comprises the K+ channel compartment and Caspr2 molecules, but also the (juxta)paranodal network between axonal and glial membranes (Gatzinsky et al., 1997). It might be important to focus future research activities on the characteristics that define the juxtaparanodal compartment as the „Achilles´ heel“ of the peripheral nerve fiber and the possible link to degenerating features implicating macrophage activation and further damage (Ip et al., 2006).
References cited:
Carenini S, Mäurer M, Werner A, Blazyca H, Toyka KV, Schmid CD, Raivich G, Martini R (2001) The role of macrophages in demyelinating peripheral nervous system of mice heterozygously deficient in P0. J Cell Biol 152:301-308.
Gatzinsky KP, Persson GH, Berthold CH (1997) Removal of retrogradely transported material from rat lumbosacral alpha-motor axons by paranodal axon-Schwann cell networks. Glia 20:115-126.
Ip CW, Kroner A, Fischer S, Berghoff M, Kobsar I, Mäurer M, Martini R (2006) Role of immune cells in animal models for inherited peripheral neuropathies. Neuromol Med 8:175-189.
Martini R, Zielasek J, Toyka KV, Giese KP, Schachner M (1995) Protein zero (P0)-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies. Nature Genet 11:281-286.
Nodari A, Previtali SC, Dati G, Occhi S, Court FA, Colombelli C, Zambroni D, Dina G, Del Carro U, Campbell KP, Quattrini A, Wrabetz L, Feltri ML (2008) alpha6beta4 integrin and dystroglycan cooperate to stabilize the myelin sheath. J Neurosci 28:6714-6719.
|
|
|
|
 |
|