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Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves.

Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, Palomo-Irigoyen M, Varela-Rey M, Griffith M, Hantke J, Macias-Camara N, Azkargorta M, Aurrekoetxea I, De Juan VG, Jefferies HB, Aspichueta P, Elortza F, Aransay AM, Martínez-Chantar ML, Baas F, Mato JM, Mirsky R, Woodhoo A, Jessen KR - J. Cell Biol. (2015)

Bottom Line: Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury.We also present evidence that myelinophagy is defective in the injured central nervous system.These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.

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Outline of myelinophagy. (left) A transverse section through a myelin Schwann cell in an uninjured nerve. Note that the myelin sheath is in direct continuity with the Schwann cell membrane and an integral component of the Schwann cell. (right) A myelin Schwann cell after nerve injury and axonal degeneration. Note that the myelin sheath has broken up into myelin fragments lying in the Schwann cell cytoplasm. The proposed role of autophagy in digesting these fragments is illustrated.
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fig8: Outline of myelinophagy. (left) A transverse section through a myelin Schwann cell in an uninjured nerve. Note that the myelin sheath is in direct continuity with the Schwann cell membrane and an integral component of the Schwann cell. (right) A myelin Schwann cell after nerve injury and axonal degeneration. Note that the myelin sheath has broken up into myelin fragments lying in the Schwann cell cytoplasm. The proposed role of autophagy in digesting these fragments is illustrated.

Mentions: Myelin destruction in injured nerves has long been recognized to take place in two phases: initially, myelin breakdown by the Schwann cells themselves, followed by myelin phagocytosis performed mostly by hematogenous macrophages (Brosius Lutz and Barres, 2014). Phagocytosis has often been suggested to be the mechanism by which Schwann cells digest their myelin, in spite of the fact that myelin is initially an intrinsic Schwann cell component (Holtzman and Novikoff, 1965; Jung et al., 2011b). While Schwann cells may well assist macrophages in phagocytosing myelin debris at later times after injury, we show here that autophagy, a mechanism by which a wide variety of cells break down their own intrinsic cellular components, is an important mechanism by which Schwann cells initiate the degradation of myelin proteins and lipids after nerve injury (Fig. 8).


Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves.

Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, Palomo-Irigoyen M, Varela-Rey M, Griffith M, Hantke J, Macias-Camara N, Azkargorta M, Aurrekoetxea I, De Juan VG, Jefferies HB, Aspichueta P, Elortza F, Aransay AM, Martínez-Chantar ML, Baas F, Mato JM, Mirsky R, Woodhoo A, Jessen KR - J. Cell Biol. (2015)

Outline of myelinophagy. (left) A transverse section through a myelin Schwann cell in an uninjured nerve. Note that the myelin sheath is in direct continuity with the Schwann cell membrane and an integral component of the Schwann cell. (right) A myelin Schwann cell after nerve injury and axonal degeneration. Note that the myelin sheath has broken up into myelin fragments lying in the Schwann cell cytoplasm. The proposed role of autophagy in digesting these fragments is illustrated.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4494002&req=5

fig8: Outline of myelinophagy. (left) A transverse section through a myelin Schwann cell in an uninjured nerve. Note that the myelin sheath is in direct continuity with the Schwann cell membrane and an integral component of the Schwann cell. (right) A myelin Schwann cell after nerve injury and axonal degeneration. Note that the myelin sheath has broken up into myelin fragments lying in the Schwann cell cytoplasm. The proposed role of autophagy in digesting these fragments is illustrated.
Mentions: Myelin destruction in injured nerves has long been recognized to take place in two phases: initially, myelin breakdown by the Schwann cells themselves, followed by myelin phagocytosis performed mostly by hematogenous macrophages (Brosius Lutz and Barres, 2014). Phagocytosis has often been suggested to be the mechanism by which Schwann cells digest their myelin, in spite of the fact that myelin is initially an intrinsic Schwann cell component (Holtzman and Novikoff, 1965; Jung et al., 2011b). While Schwann cells may well assist macrophages in phagocytosing myelin debris at later times after injury, we show here that autophagy, a mechanism by which a wide variety of cells break down their own intrinsic cellular components, is an important mechanism by which Schwann cells initiate the degradation of myelin proteins and lipids after nerve injury (Fig. 8).

Bottom Line: Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury.We also present evidence that myelinophagy is defective in the injured central nervous system.These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.

Show MeSH
Related in: MedlinePlus