Schwannomin/merlin promotes Schwann cell elongation and influences myelin segment length
Abbreviated Journal Title
Mol. Cell. Neurosci.
Schwannomin; Myelin; Cdc42; Rac; NF2; Neurofibromatosis; NF2 TUMOR-SUPPRESSOR; NEUROFIBROMATOSIS TYPE-2; P21-ACTIVATED KINASE; MERLIN PHOSPHORYLATION; PERIPHERAL-NERVES; PLASMA-MEMBRANE; ERM; ACTIVATION; GENE; GROWTH; RAC; Neurosciences
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. Published by Elsevier Inc.
Molecular and Cellular Neuroscience
"Schwannomin/merlin promotes Schwann cell elongation and influences myelin segment length" (2011). Faculty Bibliography 2010s. 1994.