Research article

Dynamic regulation of integrin activation by intracellular and extracellular signals controls oligodendrocyte morphology

Inger Marie Olsen^1,2 and Charles ffrench-Constant¹

¹  Departments of Pathology and Medical Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK

²  Centre for Basic Psychiatric Research, Aarhus University Hospital, Skovagervej 2, DK-8240 Risskov, Denmark

author email corresponding author email

BMC Biology 2005, 3:25doi:10.1186/1741-7007-3-25

Published:	12 November 2005

Abstract

Background

Myelination requires precise control of oligodendrocyte morphology and myelin generation at each of the axons contacted by an individual cell. This control must involve the integration of extracellular cues, such as those on the axon surface, with intrinsic developmental programmes. We asked whether integrins represent one class of oligodendrocyte cell-surface receptors able to provide this integration.

Results

Integrins signal via a process of activation, a conformational change that can be induced either by "outside-in" signals comprising physiological extracellular matrix ligands (mimicked by the pharmacological use of the divalent cation manganese) or "inside-out" signalling molecules such as R-Ras. Increasing levels of outside-in signalling via the laminin receptor α6β1 integrin were found to promote oligodendrocyte processing and myelin sheet formation in culture. Similar results were obtained when inside-out signalling was increased by the expression of a constitutively-active R-Ras. Inhibiting inside-out signalling by using dominant-negative R-Ras reduces processes and myelin sheets; importantly, this can be partially rescued by the co-stimulation of outside-in signalling using manganese.

Conclusion

The balance of the equilibrium between active and inactive integrins regulates oligodendrocyte morphology, which is itself regulated by extrinsic and intrinsic cues so providing a mechanism of signal integration. As laminins capable of providing outside-in signals are present on axons at the time of myelination, a mechanism exists by which morphology and myelin generation might be regulated independently in each oligodendrocyte process.