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Myelinophagy: Schwann cells dine in.

Thumm M, Simons M - J. Cell Biol. (2015)

Bottom Line: When nerve injury occurs, the axon and myelin fragments distal to the injury site have to be cleared away before repair.In this issue, Gomez-Sanchez et al. (2015; J.Cell Biol. http://dx.doi.org/10.1083/jcb.201503019) find that clearance of the damaged myelin within Schwann cells occurs not by phagocytosis but rather via selective autophagy, in a process they term "myelinophagy."

View Article: PubMed Central - HTML - PubMed

Affiliation: University Medicine, Institute of Cellular Biochemistry, University of Göttingen, D-37073 Goettingen, Germany.

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Myelinophagy. (A) Graphical illustration of a healthy myelinating Schwann cell. (B) When Wallerian degeneration is initiated, the axon starts to break down into fragments. (C) The Schwann cell then internalizes myelin fragments, possibly by the fusion of the outer “lips” of the Schwann cell plasma membrane. (D) Next, the resulting myelin fragments are taken up into phagophores. Not shown is the following: the sealing of phagophores to form autophagosomes and their fusion with lysosomes, which finally leads to degradation of the myelin fragments.
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fig1: Myelinophagy. (A) Graphical illustration of a healthy myelinating Schwann cell. (B) When Wallerian degeneration is initiated, the axon starts to break down into fragments. (C) The Schwann cell then internalizes myelin fragments, possibly by the fusion of the outer “lips” of the Schwann cell plasma membrane. (D) Next, the resulting myelin fragments are taken up into phagophores. Not shown is the following: the sealing of phagophores to form autophagosomes and their fusion with lysosomes, which finally leads to degradation of the myelin fragments.

Mentions: To solve this topological conundrum, a closer look at myelin architecture is necessary. Myelin is formed when the “inner tongue,” the leading edge of the myelinating cells, starts to move multiple times around the axon until a multilayered compacted membrane is generated (Bunge et al., 1989; Snaidero et al., 2014). When the process is completed, the Schwann cell engulfs the myelin sheath with its outermost, cytoplasmic-rich myelin layer (Fig. 1 A). Even if myelin is localized within the interior of the Schwann cell, it is continuous with the plasma membrane and therefore not an intracellular structure. However, in nerves undergoing Wallerian degeneration (Fig. 1 B), myelin starts to fragment into ovoid-like structures in an active process that requires actin polymerization at the Schmidt-Lanterman incisures (Jung et al., 2011). During this process, myelin loses its connection with the cell surface (Fig. 1 C). If, now, the outermost layer of the myelin membrane fuses with the plasma membrane—like the closure of a phagocytic cup—fragmented myelin would be internalized into the Schwann cell cytoplasm without using endocytic pathways. Here, the myelin fragments could be selectively recognized by so-far unknown autophagic receptor molecules for the recruitment to the phagophore (Fig. 1 D). Why do Schwann cells use autophagy and not endocytosis for recycling parts of its plasma membrane? One reason could be that fragmented myelin sheaths are too tightly clumped and too bulky for Schwann cells that are not specialized in phagocytosis.


Myelinophagy: Schwann cells dine in.

Thumm M, Simons M - J. Cell Biol. (2015)

Myelinophagy. (A) Graphical illustration of a healthy myelinating Schwann cell. (B) When Wallerian degeneration is initiated, the axon starts to break down into fragments. (C) The Schwann cell then internalizes myelin fragments, possibly by the fusion of the outer “lips” of the Schwann cell plasma membrane. (D) Next, the resulting myelin fragments are taken up into phagophores. Not shown is the following: the sealing of phagophores to form autophagosomes and their fusion with lysosomes, which finally leads to degradation of the myelin fragments.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4494007&req=5

fig1: Myelinophagy. (A) Graphical illustration of a healthy myelinating Schwann cell. (B) When Wallerian degeneration is initiated, the axon starts to break down into fragments. (C) The Schwann cell then internalizes myelin fragments, possibly by the fusion of the outer “lips” of the Schwann cell plasma membrane. (D) Next, the resulting myelin fragments are taken up into phagophores. Not shown is the following: the sealing of phagophores to form autophagosomes and their fusion with lysosomes, which finally leads to degradation of the myelin fragments.
Mentions: To solve this topological conundrum, a closer look at myelin architecture is necessary. Myelin is formed when the “inner tongue,” the leading edge of the myelinating cells, starts to move multiple times around the axon until a multilayered compacted membrane is generated (Bunge et al., 1989; Snaidero et al., 2014). When the process is completed, the Schwann cell engulfs the myelin sheath with its outermost, cytoplasmic-rich myelin layer (Fig. 1 A). Even if myelin is localized within the interior of the Schwann cell, it is continuous with the plasma membrane and therefore not an intracellular structure. However, in nerves undergoing Wallerian degeneration (Fig. 1 B), myelin starts to fragment into ovoid-like structures in an active process that requires actin polymerization at the Schmidt-Lanterman incisures (Jung et al., 2011). During this process, myelin loses its connection with the cell surface (Fig. 1 C). If, now, the outermost layer of the myelin membrane fuses with the plasma membrane—like the closure of a phagocytic cup—fragmented myelin would be internalized into the Schwann cell cytoplasm without using endocytic pathways. Here, the myelin fragments could be selectively recognized by so-far unknown autophagic receptor molecules for the recruitment to the phagophore (Fig. 1 D). Why do Schwann cells use autophagy and not endocytosis for recycling parts of its plasma membrane? One reason could be that fragmented myelin sheaths are too tightly clumped and too bulky for Schwann cells that are not specialized in phagocytosis.

Bottom Line: When nerve injury occurs, the axon and myelin fragments distal to the injury site have to be cleared away before repair.In this issue, Gomez-Sanchez et al. (2015; J.Cell Biol. http://dx.doi.org/10.1083/jcb.201503019) find that clearance of the damaged myelin within Schwann cells occurs not by phagocytosis but rather via selective autophagy, in a process they term "myelinophagy."

View Article: PubMed Central - HTML - PubMed

Affiliation: University Medicine, Institute of Cellular Biochemistry, University of Göttingen, D-37073 Goettingen, Germany.

Show MeSH
Related in: MedlinePlus