Asymmetric ERM activation at the Schwann cell process tip is required in axon-associated motility.
Axon-associated Schwann cell (SC) motility and process dynamics are crucial in the development and regeneration of the peripheral nervous system (PNS). The bipolar morphology of SCs represents an unexplored conundrum in terms of directed motility. Using fluorescence time-lapse microscopy of transfected SCs within myelinating dorsal root ganglion (DRG) explants, we demonstrate cycling of SCs between bipolar and highly motile, unipolar morphologies as a result of asymmetric process retraction and extension. Unipolar SC motility appears nucleotaxic in nature, similar to the movement of neurons on radial glia during cortical development. We also show that asymmetric process retraction is associated with the activation of ERM (ezrin/radixin/moesin) proteins and subsequent recruitment of ezrin-binding phospho-protein 50 kDa (EBP50) at the retracting process tip. This activation occurs in response to localized synthesis of phosphatidylinositol (4,5)-bisphosphate (PIP2) at this site. Finally, we demonstrate that the activation of ERM proteins at the SC process tip is essential for motility and the maintenance of SC polarity, as ERM disruption yields a dysfunctional, multi-polar cell. These results demonstrate that specializations at the tips of SC processes regulate their dynamics, which in turn is associated with directed motility in these cells.
Gatto
Cheryl L
CL
Department of Cell Biology, Programs in Neuroscience and Cell Dynamics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Walker
Barbara J
BJ
Lambert
Stephen
S
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism* / Q000502:physiology; D049452:Green Fluorescent Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism* / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers; D013997:Time Factors; D046509:Tissue Culture Techniques; D014162:Transfection; D000099149:Ezrin
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D049452:Green Fluorescent Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D017923:Sodium-Hydrogen Exchangers; D000099149:Ezrin; C093376:sodium-hydrogen exchanger regulatory factor; C071058:moesin; C071776:radixin