Title

Asymmetric ERM activation at the Schwann cell process tip is required in axon-associated motility

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

10-25-2006

Document Type

Article

Medical Subject Headings

Animals; Axons; Carrier Proteins; *Cell Movement; Cell Polarity; Cytoskeletal Proteins; Ganglia, Spinal; Green Fluorescent Proteins; Membrane Proteins; Microfilament Proteins; Microscopy, Fluorescence; Microscopy, Video; Phosphatidylinositol 4,5-Diphosphate; Phosphoproteins; Rats; Rats, Wistar; Recombinant Fusion Proteins; Schwann Cells; Time Factors; Tissue Culture Techniques; Transfection

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: J Cell Physiol. 2007 Jan;210(1):122-32. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

17061246