Ral GTPases in Schwann cells promote radial axonal sorting in the peripheral nervous system.
Andrea OmmerGianluca FigliaJorge A PereiraAnna Lena DatwylerJoanne GerberJonathan DeGeerGiovanna LalliUeli SuterPublished in: The Journal of cell biology (2019)
Small GTPases of the Rho and Ras families are important regulators of Schwann cell biology. The Ras-like GTPases RalA and RalB act downstream of Ras in malignant peripheral nerve sheath tumors. However, the physiological role of Ral proteins in Schwann cell development is unknown. Using transgenic mice with ablation of one or both Ral genes, we report that Ral GTPases are crucial for axonal radial sorting. While lack of only one Ral GTPase was dispensable for early peripheral nerve development, ablation of both RalA and RalB resulted in persistent radial sorting defects, associated with hallmarks of deficits in Schwann cell process formation and maintenance. In agreement, ex vivo-cultured Ral-deficient Schwann cells were impaired in process extension and the formation of lamellipodia. Our data indicate further that RalA contributes to Schwann cell process extensions through the exocyst complex, a known effector of Ral GTPases, consistent with an exocyst-mediated function of Ral GTPases in Schwann cells.
Keyphrases
- peripheral nerve
- induced apoptosis
- single cell
- cell therapy
- cell cycle arrest
- spinal cord injury
- traumatic brain injury
- wild type
- endoplasmic reticulum stress
- cell death
- immune response
- ultrasound guided
- machine learning
- signaling pathway
- regulatory t cells
- dna methylation
- endothelial cells
- genome wide
- dendritic cells
- cell proliferation