αV integrins in Schwann cells promote attachment to axons, but are dispensable in vivo

Abstract

In the developing peripheral nervous system, Schwann cells (SCs) extend their processes to contact, sort, and myelinate axons. The mechanisms that contribute to the interaction between SCs and axons are just beginning to be elucidated. Using a SC-neuron coculture system, we demonstrate that Arg-Gly-Asp (RGD) peptides that inhibit α_V -containing integrins delay the extension of SCs elongating on axons. α_V integrins in SC localize to sites of contact with axons and are expressed early in development during radial sorting and myelination. Short interfering RNA-mediated knockdown of the α_V integrin subunit also delays SC extension along axons in vitro, suggesting that α_V -containing integrins participate in axo-glial interactions. However, mice lacking the α_V subunit in SCs, alone or in combination with the potentially compensating α₅ subunit, or the α_V partners β₃ or β₈ , myelinate normally during development and remyelinate normally after nerve crush, indicating that overlapping or compensatory mechanisms may hide the in vivo role of RGD-binding integrins.

Keywords: RGD; Schwann cell; axo-glial interactions; integrin; lamellipodia; process extension.