Myelin: A One-Dimensional Biological “Crystal” for X-Ray and Neutron Scattering - Molecules: Nucleation, Aggregation and Crystallization - page 78

(Kirschner, Blaurock, 1992). The electron density profile for this 1D lat-
tice, which can be calculated from the X-ray diffraction data, confirms
that the myelin consists of lipid bilayers, and provides a measure of the widths
of the extracellular and cytoplasmic spaces (Finean, Burge, 1963; Moody,
1963; Blaurock et al ., 1971; Caspar, Kirschner, 1971; McIntosh, Worthington,
1974; Inouye et al ., 1989; Luzzati, Mateu, 1990; Mateu et al ., 1990).
The disruption of myelinated tissue in the CNS and PNS results in
nerve conduction abnormalities including transmission failure, and corre-
lates with neurological disorders including multiple sclerosis, peroxiso-
mal dysfunction, and peripheral neuropathies. Mutations in genes that
encode myelin or myelin-related proteins or lipids can cause serious neu-
rological disorders via amyelination or dysmyelination — i.e. the failure
of formation or abnormal formation of myelin — during development, or
eventual demyelination (breakdown of myelin). For example, the severe
CNS leukodystrophy known as Pelizaeus-Merzbacher disease is caused
by mutations in myelin proteolipid protein; and PNS demyelinating neu-
ropathies having varying phenotypes (or observable characteristics at the
clinical, morphological, or biochemical level) such as Charcot-Marie-
Tooth disease and Dejerine-Sottas syndrome are caused by mutations in
the genes for myelin protein zero (P0 glycoprotein), PMP22, and others
(Lazzarini, 2004). Many of these correlate with myelin packing defects
and lattice instability (Avila et al ., 2005; Wrabetz et al ., 2006).
The compact extracellular apposition in PNS myelin under native
conditions (i.e. physiological pH and ionic strength) is stabilized by con-
tacts between P0 molecules, most likely involving ionic interactions of
histidine residues (Inouye, Kirschner, 1988). The packing of myelin mem-
branes to form the multilamellar sheath (Fig. 1), however, is not static but
rather dynamic (Uzman, Hedley-Whyte, 1968). The inter-membrane sep-
aration at the extracellular apposition is highly labile, and the swelling and
compaction here as a function of pH and ionic strength can be accounted
for by the DLVO (Derjaguin, Landau, Verwey and Overbeek) theory of
colloid stability (Verwey, Overbeek, 1948). By contrast, the cytoplasmic
apposition is invariant over a wide range of pH and ionic strength. What
underlies this relative stability has been enigmatic; however, recent studies