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 alpha(V)-containing integrins delay the extension of SCs elongating on axons. alpha(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 alpha(V)integrin subunit also delays SC extension along axons in vitro, suggesting that alpha(V)-containing integrins participate in axo-glial interactions. However, mice lacking the alpha(V)subunit in SCs, alone or in combination with the potentially compensating alpha(5)subunit, or the alpha(V)partners beta(3)or beta(8), 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.
αV integrins in Schwann cells promote attachment to axons, but are dispensable in vivo [alpha(V)integrins in Schwann cells promote attachment to axons, but are dispensable in vivo] / K.K. Catignas, L.R. Frick, M. Pellegatta, E. Hurley, Z. Kolb, K. Addabbo, J.H. Mccarty, R.O. Hynes, A. van der Flier, Y. Poitelon, L. Wrabetz, M.L. Feltri. - In: GLIA. - ISSN 1098-1136. - 69:1(2021 Jan), pp. 91-108. [10.1002/glia.23886]
αV integrins in Schwann cells promote attachment to axons, but are dispensable in vivo [alpha(V)integrins in Schwann cells promote attachment to axons, but are dispensable in vivo]
M.L. Feltri
Ultimo
Supervision
2021
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 alpha(V)-containing integrins delay the extension of SCs elongating on axons. alpha(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 alpha(V)integrin subunit also delays SC extension along axons in vitro, suggesting that alpha(V)-containing integrins participate in axo-glial interactions. However, mice lacking the alpha(V)subunit in SCs, alone or in combination with the potentially compensating alpha(5)subunit, or the alpha(V)partners beta(3)or beta(8), 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.File | Dimensione | Formato | |
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