title: Schwann cell spectrins modulate peripheral nerve myelination.
abstract: During peripheral nerve development, Schwann cells ensheathe axons and form myelin to enable rapid and efficient action potential propagation. Although myelination requires profound changes in Schwann cell shape, how neuron-glia interactions converge on the Schwann cell cytoskeleton to induce these changes is unknown. Here, we demonstrate that the submembranous cytoskeletal proteins αII and βII spectrin are polarized in Schwann cells and colocalize with signaling molecules known to modulate myelination in vitro. Silencing expression of these spectrins inhibited myelination in vitro, and remyelination in vivo. Furthermore, myelination was disrupted in motor nerves of zebrafish lacking αII spectrin. Finally, we demonstrate that loss of spectrin significantly reduces both F-actin in the Schwann cell cytoskeleton and the Nectin-like protein, Necl4, at the contact site between Schwann cells and axons. Therefore, we propose αII and βII spectrin in Schwann cells integrate the neuron-glia interactions mediated by membrane proteins into the actin-dependent cytoskeletal rearrangements necessary for myelination.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Susuki
authors.forename: Alya R
authors.initials: AR
authors.lastname: Raphael
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stankewich
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
authors.forename: William S
authors.initials: WS
authors.lastname: Talbot
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Rasband
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D016764:Cell Polarity; D003599:Cytoskeleton / Q000502:physiology; D055785:Gene Knockdown Techniques; D009154:Mutation; D009186:Myelin Sheath / Q000502:physiology*; D010525:Peripheral Nerves / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries / Q000502:physiology; D013049:Spectrin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D000199:Actins; D029961:Zebrafish Proteins; D013049:Spectrin