Peripheral myelin of Xenopus laevis: Role of electrostatic and hydrophobic interactions in membrane compaction

Abstract

P0 glycoprotein is the major structural protein of peripheral nerve myelin where it is thought to modulate inter-membrane adhesion at both the extracellular apposition, which is labile upon changes in pH and ionic strength, and the cytoplasmic apposition, which is resistant to such changes. Most studies on P0 have focused on structure-function correlates in higher vertebrates. Here, we focused on its role in the structure and interactions of frog (Xenopus laevis) myelin, where it exists primarily in a dimeric form. As part of our study, we deduced the full sequence of Xenopus laevis P0 (xP0) from its cDNA. The xP0 sequence was found to be similar to P0 sequences of higher vertebrates, suggesting that a common mechanism of PNS myelin compaction via P0 interaction might have emerged through evolution. As previously reported for mouse PNS myelin, a similar change of extracellular apposition in frog PNS myelin as a function of pH and ionic strength was observed, which can be explained by a conformational change of P0 due to protonation-deprotonation of His52 at P0's putative adhesive interface. On the other hand, the cytoplasmic apposition in frog PNS myelin, like that in the mouse, remained unchanged at different pH and ionic strength. The contribution of hydrophobic interactions to stabilizing the cytoplasmic apposition was tested by incubating sciatic nerves with detergents. Dramatic expansion at the cytoplasmic apposition was observed for both frog and mouse, indicating a common hydrophobic nature at this apposition. Urea also expanded the cytoplasmic apposition of frog myelin likely owing to denaturation of P0. Removal of the fatty acids that attached to the single Cys residue in the cytoplasmic domain of P0 did not change PNS myelin structure of either frog or mouse, suggesting that the P0-attached fatty acyl chain does not play a significant role in PNS myelin compaction and stability. These results help clarify the present understanding of P0's adhesion role and the role of its acylation in compact PNS myelin.

Analysis of Peripheral Nerve Expression Profiles Identifies a Novel Myelin Glycoprotein, MP11

“…Coincidentally, the lower vertebrates in which Mp11 is expressed, such as zebrafish and frog, also possess well developed myelin sheaths, including myelination of peripheral nerves (Avila et al, 2007) (Luo et al, 2007). Furthermore, zebrafish and frog express other critically important myelin proteins such as Mpz, Mbp and Pmp22 lending more evidence that Mp11 may be an evolutionarily conserved essential component of myelin.…”

Correlated Disorder in Myelinated Axons Orientational Geometry and Structure

“…The unit of the myelin multi-lamellar ultrastructure is shown in Figure 1b. It is made of the stacking of (i) one cytoplasmatic apposition (cyt), (ii) one lipidic membrane (lpg), (iii) one extracellular apposition (ext), and (iv) another lipidic mambrane (lpg) [3][4][5] …”

“…It has a periodic multi-lamellar structure, whose unit is made up of the repetition of four layers: cytoplasmic apposition of Schwann cells (cyt), lipidic membrane (lpg) extracellular apposition of Schwann cells (ext) and another lipidic membrane (lpg). The available information about the myelin layers has been extracted from measurements performed by space averaged laboratory X-Ray Diffraction (XRD) [3][4][5][6], electron microscopy (EM) [6,7] and neutron diffraction [8].…”

Myelin structure and composition of myelinated tissue in the African lungfish

“…The membrane packing in myelin is defined by a combination of non-specific and specific interactions that stabilize the close apposition of the membranes at both the cytoplasmic and extracellular boundaries (Inouye and Kirschner, 1988a,b;Luo et al, 2007Luo et al, , 2008Min et al, 2009). To probe these interactions, we subjected the lungfish nerves to 'electrostatic stressing' by changing the pH and ionic strength of the incubation medium (Fig.…”

“…Data for teleost (zebrafish, 'Jack Dempsey', goldfish), amphibia (mudpuppy, bullfrog, frog) and mouse were taken from other studies (Blaurock, 1967;Kirschner et al, 1989;Avila et al, 2005Avila et al, , 2007Luo et al, 2008). Analysis of the lipids isolated from myelinated tissues showed that the lungfish lacked hydroxy-fatty acids, and that fatty acid chain length and degree of saturation did not differ markedly from those in a limited phylogenetic series.…”