title: Schwannomin/merlin promotes Schwann cell elongation and influences myelin segment length.
abstract: The Neurofibromatosis type 2 tumor suppressor, schwannomin (Sch) is a plasma membrane-cytoskeleton linking protein that regulates receptor signaling and actin dynamics. We examined Sch's role in specifying morphological changes needed for Schwann cell (SC) function in vitro. Isolated Sch-GFP-expressing SCs extended bipolar processes 82% longer than those formed by GFP-expressing cells. In contrast, SCs expressing dominant negative Sch-BBA-GFP extended bipolar processes 16% shorter than controls and 64% shorter than Sch-GFP-expressing SCs. nf2 gene inactivation caused isolated mouse SCs to transition from bipolar to multipolar cells. Live imaging revealed that SCs co-expressing Sch-GFP and dominant negative RacN17 behaved similarly in dorsal root ganglion explant cultures; they quickly aligned on axons and slowly elongated bipolar processes. In contrast, SCs expressing constitutively active RacV12 underwent continuous transitions in morphology that interfered with axon alignment. When co-cultured with neurons under myelin-promoting conditions, Sch-GFP-expressing SCs elaborated longer myelin segments than GFP-expressing SCs. In contrast, Sch-BBA-GFP-expressing SCs failed to align on or myelinate axons. Together, these results demonstrate that Sch plays an essential role in inducing and/or maintaining the SC's spindle shape and suggest that the mechanism involves Sch-dependent inhibition of Rac activity. By stabilizing the bipolar morphology, Sch promotes the alignment of SCs with axons and ultimately influences myelin segment length.
authors.affiliation: Department of Molecular Biology and Microbiology, Burnett School of Biomedical Science, College of Medicine, University of Central Florida, Health Science Campus, 6900 Lake Nona Boulevard, Orlando, FL 32827, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Thaxton
authors.forename: Marga
authors.initials: M
authors.lastname: Bott
authors.forename: Barbara
authors.initials: B
authors.lastname: Walker
authors.forename: Nicklaus A
authors.initials: NA
authors.lastname: Sparrow
authors.forename: Stephen
authors.initials: S
authors.lastname: Lambert
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernandez-Valle
mesh_terms: D000086:Acetazolamide; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure*; D016518:Neurofibromatosis 2 / Q000378:metabolism; D025581:Neurofibromin 2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D025581:Neurofibromin 2; D011993:Recombinant Fusion Proteins; D020744:rac GTP-Binding Proteins; D000086:Acetazolamide