scholarly journals Cdc42 regulates schwann cell radial sorting and myelin sheath folding through NF2/merlin-dependent and independent signaling

Glia ◽  
2013 ◽  
Vol 61 (11) ◽  
pp. 1906-1921 ◽  
Author(s):  
Li Guo ◽  
Chandra Moon ◽  
Yi Zheng ◽  
Nancy Ratner
Glia ◽  
2011 ◽  
Vol 59 (7) ◽  
pp. 1047-1055 ◽  
Author(s):  
Alya R. Raphael ◽  
David A. Lyons ◽  
William S. Talbot

1962 ◽  
Vol 40 (1) ◽  
pp. 1261-1271
Author(s):  
L. S. Wolfe

Recent investigations have demonstrated that cellular and intracellular membranes within the nervous system contain complex associations of lipids, proteins, and carbohydrates. The myelin sheath contains such complexes derived from the Schwann cell or satellite cell membranes. Similar complexes are found in membranes from grey matter together with less familiar associations between lipids and carbohydrates. Gangliosides are a group of acidic glycolipids which contain among other sugars the sialic acid, N-acetylneuraminic acid. The present state of knowledge on the chemical structure, metabolism, and functional importance of these complex macromolecules is discussed.


1973 ◽  
Vol 58 (1) ◽  
pp. 42-53 ◽  
Author(s):  
Frank A. Rawlins

A time-sequence study of the incorporation and distribution of cholesterol in peripheral nerve myelin was carried out by electron microscope autoradiography. [1,2-3H]Cholesterol was injected into 10-day old mice and the sciatic nerves were dissected out at 10, 20, 40, 60, 90, 120, and 180 min after the injection. 20 min after injection the higher densities of grains due to the presence of [3H]cholesterol were confined to the outer and inner edges of the myelin sheath. Practically no cholesterol was detected in the midzone of the myelin sheath. 1 ½ h after injection, cholesterol showed a wider distribution within the myelin sheath, the higher densities of grains occurring over the two peripheral myelin bands, each approximately 3,100 Å wide. Cholesterol was also present in the center of the myelin sheath but to a considerably lesser extent. 3 h after injection cholesterol appeared homogeneously distributed within the myelin sheath. Schwann cell and axon compartments were also labeled at each time interval studied beginning 20 min postinjection. These observations indicate that preformed cholesterol enters myelin first and almost simultaneously through the inner and outer edges of the sheath; only after 90 min does the density of labeled cholesterol in the central zone of myelin reach the same density as that in the outer and inner zones. These findings suggest that cholesterol used by the nerve fibers in the formation and maintenance of the myelin sheath enters the lamellae from the Schwann cell cytoplasm and from the axon. The possibility of a bidirectional movement of molecules, i.e. from the Schwann cell to the axon and from the axon to the Schwann cell through the myelin sheath, is noted. The results are discussed in the light of recent observations on the exchange, reutilization, and transaxonal movement of cholesterol.


Glia ◽  
2017 ◽  
Vol 65 (9) ◽  
pp. 1452-1470 ◽  
Author(s):  
Anne M. Logan ◽  
Anna E. Mammel ◽  
Danielle C. Robinson ◽  
Andrea L. Chin ◽  
Alec F. Condon ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria A. Eichel ◽  
Vasiliki-Ilya Gargareta ◽  
Elisa D’Este ◽  
Robert Fledrich ◽  
Theresa Kungl ◽  
...  

Abstract The velocity of nerve conduction is moderately enhanced by larger axonal diameters and potently sped up by myelination of axons. Myelination thus allows rapid impulse propagation with reduced axonal diameters; however, no myelin-dependent mechanism has been reported that restricts radial growth of axons. By label-free proteomics, STED-microscopy and cryo-immuno electron-microscopy we here identify CMTM6 (chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6) as a myelin protein specifically localized to the Schwann cell membrane exposed to the axon. We find that disruption of Cmtm6-expression in Schwann cells causes a substantial increase of axonal diameters but does not impair myelin biogenesis, radial sorting or integrity of axons. Increased axonal diameters correlate with accelerated sensory nerve conduction and sensory responses and perturbed motor performance. These data show that Schwann cells utilize CMTM6 to restrict the radial growth of axons, which optimizes nerve function.


Author(s):  
Roy O. Weller

The length of axon that each Schwann cell myelinates in a normal peripheral nerve is approximately proportional to the diameter of the axon and the thickness of the myelin sheath produced. When segmental demyelination occurs, individual segments, represented by the length of axon covered by one Schwann cell, lose their myelin sheaths but the axons are preserved. This differs from Wallerian degeneration where myelin destruction occurs along the length of a nerve fibre following death of the axon.In experimental diphtheritic neuropathy, an acute segmental demyelinating disease, lysosomes accumulate within the Schwann cells prior to disruption of the myelin sheath; furthermore, the site of initial myelin breakdown appears to be closely related to the collections of lysosomes. The Schwann cell starts to form a new myelin sheath around the axon probably within a few hours of the destruction of the original myelin sheath, and while the latter is being catabolised within lysosomal vacuoles This stage of remyelination follows a similar course to primary myelination, so that the recovery stage is characterised by normal axons with either no myelin, or surrounded by sheaths that are very thin relative to the diameter of the axon.


1971 ◽  
Vol 8 (2) ◽  
pp. 541-555
Author(s):  
SUSAN M. HALL ◽  
P. L. WILLIAMS

Two electron-dense tracers, ferritin and lanthanum, have been administered to peripheral nerve fibres, and their uptake has been studied ultrastructurally. It was found that the perineurium was an effective barrier to ferritin in vivo, and the tracer was subsequently injected sub-perineurially. Ferritin uptake over a 120-min period was confined to occasional phagocytic vesicles in perineurial and Schwann cells, and to the nodal gap substance and paranodal periaxonal space. No uptake was observed in the myelin sheath, incisural intraperiod line gap, or in the axoplasm. Soaking fibres in ferritin in vitro resulted in a more generalized cytoplasmic and axoplasmic uptake, although the myelin sheath and Schmidt-Lanterman incisures remained devoid of the tracer. Lanthanum nitrate, included in the fixative solution, delineated the patent incisural intraperiod line gap, and outlined the external surface of the terminal loops of nodal Schwann cell cytoplasm, and the paranodal Schwann cell-axolemmal junction. Unlike ferritin, La3+ penetrated the myelin sheath, being usually confined to the intraperiod line region of the outer lamellae, where it was associated with a widening of the lamellar unit, and an apparent splitting of the intraperiod line. The results are discussed with regard to distribution of extracellular space in peripheral nerve fibres.


Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 4265-4273 ◽  
Author(s):  
S.S. Scherer ◽  
Y.T. Xu ◽  
P.G. Bannerman ◽  
D.L. Sherman ◽  
P.J. Brophy

Periaxin is a newly described protein that is expressed exclusively by myelinating Schwann cells. In developing nerves, periaxin is first detected as Schwann cells ensheathe axons, prior to the appearance of the proteins that characterize the myelin sheath. Periaxin is initially concentrated in the adaxonal membrane (apposing the axon) but, during development, as myelin sheaths mature, periaxin becomes predominately localized at the abaxonal Schwann cell membrane (apposing the basal lamina). In permanently axotomized adult nerves, periaxin is lost from the abaxonal and adaxonal membranes, becomes associated with degenerating myelin sheaths and is phagocytosed by macrophages. In crushed nerves, in which axons regenerate and are remyelinated, periaxin is first detected in the adoxonal membrane as Schwann cells ensheathe regenerating axons, but again prior to the appearance of other myelin proteins. Periaxin mRNA and protein levels change in parallel with those of other myelin-related genes after permanent axotomy and crush. These data demonstrate that periaxin is expressed by myelinating Schwann cells in a dynamic, developmentally regulated manner. The shift in localization of periaxin in the Schwann cell after completion of the spiralization phase of myelination suggests that periaxin participates in membrane-protein interactions that are required to stabilize the mature myelin sheath.


2007 ◽  
Vol 177 (6) ◽  
pp. 1051-1061 ◽  
Author(s):  
Yves Benninger ◽  
Tina Thurnherr ◽  
Jorge A. Pereira ◽  
Sven Krause ◽  
Xunwei Wu ◽  
...  

During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue-specific conditional gene targeting to show that members of the Rho GTPases, cdc42 and rac1, have different and essential roles in axon sorting by Schwann cells. Our results indicate that although cdc42 is required for normal Schwann cell proliferation, rac1 regulates Schwann cell process extension and stabilization, allowing efficient radial sorting of axon bundles.


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