Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork.
Myelin membrane assembly is driven by a phase transition of myelin basic proteins into a cohesive protein meshwork.
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DOI：
10.1371/journal.pbio.1001577
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发表时间：
2013
期刊：
影响因子：
9.8
通讯作者：
Simons M
中科院分区：
文献类型：
--
作者：
Aggarwal S;Snaidero N;Pähler G;Frey S;Sánchez P;Zweckstetter M;Janshoff A;Schneider A;Weil MT;Schaap IA;Görlich D;Simons M
Myelin basic protein undergoes a phase transition from a cytoplasmic soluble pool into a cohesive functional amyloid-like assembly; this may be one mechanism of myelin membrane biogenesis. Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system. Myelin is a specialized membrane that covers axons and serves as an insulator to enable the fast conduction of the action potentials. The importance of myelin membrane is highlighted in demyelinating diseases such as multiple sclerosis, which lead to severe neurological disability. Here, we describe a physicochemical mechanism of how myelin is generated and assembled. We find that myelin basic protein (MBP) molecules undergo a phase transition into a cohesive meshwork at the membrane interface, which drives structural changes in the membranes. We provide evidence that the interaction of myelin basic proteins with the inner leaflet of the myelin bilayer results in charge neutralization and triggers self-association of the protein into larger polymers. Interactions between MBP molecules are mediated by hydrophobic phenylalanine residues and amyloid-like association. We propose that phase transition of MBP from a cytoplasmic soluble pool into a cohesive functional amyloid-like assembly is one of the key mechanisms in myelin membrane biogenesis.
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DOI：
10.1073/pnas.0910163107
发表时间：
2010-04-06
影响因子：
11.1
作者：
Ader, Christian;Frey, Steffen;Baldus, Marc
通讯作者：
Baldus, Marc
影响因子：
56.9
作者：
Frey, Steffen;Richter, Ralf P.;Goerlich, Dirk
通讯作者：
Goerlich, Dirk
影响因子：
64.8
作者：
Friedrichson, T;Kurzchalia, TV
通讯作者：
Kurzchalia, TV
影响因子：
11.4
作者：
Alexander, Robert Todd;Jaumouille, Valentin;Grinstein, Sergio
通讯作者：
Grinstein, Sergio
影响因子：
7.7
作者：
Eisele, Nico B.;Frey, Steffen;Piehler, Jacob;Goerlich, Dirk;Richter, Ralf P.
通讯作者：
Richter, Ralf P.