Abstract
The formation of a mature myelin sheath in the vertebrate nervous system requires specific protein-membrane interactions. Several myelin-specific proteins are involved in stacking lipid membranes into multilayered structures around axons, and misregulation of these processes may contribute to chronic demyelinating diseases. Two key proteins in myelin membrane binding and stacking are the myelin basic protein (MBP) and protein zero (P0). Other factors, including Ca2+, are important for the regulation of myelination. We studied the effects of ionic strength and Ca2+ on the membrane interactions of MBP and the cytoplasmic domain of P0 (P0ct). MBP and P0ct bound and aggregated negatively charged lipid vesicles, while simultaneously folding, and both ionic strength and calcium had systematic effects on these interactions. When decreasing membrane net negative charge, the level and kinetics of vesicle aggregation were affected by both salt and Ca2+. The effects on lipid membrane surfaces by ions can directly affect myelin protein-membrane interactions, in addition to signalling effects in myelinating glia.
Highlights
Myelin contributes to the efficiency of both the central and peripheral nervous system (CNS and PNS, respectively) via axonal insulation and trophic support [1,2]
Myelination requires a balance between myelin protein expression, protein-membrane interactions, and regulatory factors, such as calcium
Both myelin basic protein (MBP) and P0ct are intrinsically disordered protein (IDP) in solution, but upon binding to membranes, they fold into helical structures, altering the physical properties of the membrane [13,17,18,28,33]
Summary
Myelin contributes to the efficiency of both the central and peripheral nervous system (CNS and PNS, respectively) via axonal insulation and trophic support [1,2]. MBP carries a positive charge and presents post-translationally citrullinated forms with differing net charge [19] It requires negatively charged lipids for membrane adhesion, but correct myelin morphology depends on other lipids and ions [10,18,20]. Like MBP, P0ct is positively charged and interacts with phospholipids through electrostatics, gaining secondary structure [27,28]. This might make it susceptible to effects caused by cationic species. We studied the effects of ionic strength and Ca2þ on the structural and functional aspects of MBP and P0ct binding to membranes using biophysical techniques. Raasakka et al / Biochemical and Biophysical Research Communications 511 (2019) 7e12
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