title: Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration.
abstract: The mechanisms that trigger Wallerian degeneration (WD) of peripheral nerves after injury are not well understood. During the early period of WD, fragmentation of myelin into ovoid structures occurs near the Schmidt-Lantermann incisures (SLI), a noncompact region of the myelin sheath containing autotypical adherens junction. In this study, we found that new filamentous actin polymerization occurs in the SLI of mouse sciatic nerves after injury and that its inhibition prevented not only the degradation of E-cadherin in the SLI but also myelin ovoid formation. However, the inhibition of actin polymerization could not block Schwann cell dedifferentiation. The activation of Rac GTPase was observed in the distal stump of the injured nerves, and a specific Rac inhibitor, a dominant-negative Rac, and Rac1-RNA interference blocked myelin ovoid formation. Together, these findings suggest that dynamic changes in actin in the SLI are essential for initiation of demyelination after peripheral nerve injury.
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 602-714, South Korea.
authors.forename: Junyang
authors.initials: J
authors.lastname: Jung
authors.forename: Wenting
authors.initials: W
authors.lastname: Cai
authors.forename: Hyun Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Marta
authors.initials: M
authors.lastname: Pellegatta
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Shin
authors.forename: So Young
authors.initials: SY
authors.lastname: Jang
authors.forename: Duk Joon
authors.initials: DJ
authors.lastname: Suh
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
authors.forename: M Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Hwan Tae
authors.initials: HT
authors.lastname: Park
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D019771:Axotomy; D015820:Cadherins / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004195:Disease Models, Animal; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism; D018274:Electroporation / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018993:Myelin P0 Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics; D009924:Organ Culture Techniques; D058105:Polymerization; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D012584:Sciatic Nerve / Q000473:pathology*; D013997:Time Factors; D014855:Wallerian Degeneration / Q000473:pathology* / Q000503:physiopathology; D020744:rac GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics; D020830:rac1 GTP-Binding Protein
chemical_list: D000199:Actins; D000634:Aminoquinolines; D015820:Cadherins; D051767:Early Growth Response Protein 2; D018993:Myelin P0 Protein; C487513:NSC 23766; D009479:Neuropeptides; D011500:Protein Synthesis Inhibitors; D011743:Pyrimidines; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; D049452:Green Fluorescent Proteins; D003513:Cycloheximide; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein