Astrocytic α vβ 3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering thy-1

Herrera-Molina R, Frischknecht R, Maldonado H, Seidenbecher CI, Gundelfinger ED, Hetz C, De La Luz Aylwin M, Schneider P, Quest AFG, Leyton L (2012)

Publication Type: Journal article

Publication year: 2012

Journal

PLoS ONE Public Library of Science

Book Volume: 7

Article Number: e34295

Journal Issue: 3

DOI: 10.1371/journal.pone.0034295

Abstract

Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to α Vβ 3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether α Vβ 3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of α Vβ 3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous α Vβ 3 integrin restricted neurite outgrowth. Likewise, α Vβ 3-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(-) CAD cells. In differentiating primary neurons exposed to α Vβ 3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, α Vβ 3-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by α Vβ 3 integrin. Binding of α Vβ 3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, α Vβ 3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that α Vβ 3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.

Involved external institutions

Universidad de Santiago de Chile (USACH) / University of Santiago, Chile CL Chile (CL) Max-Planck-Institut für Neurobiologie / Max Planck Institute of Neurobiology DE Germany (DE) Université de Lausanne (UNIL) CH Switzerland (CH)

How to cite

APA:

Herrera-Molina, R., Frischknecht, R., Maldonado, H., Seidenbecher, C.I., Gundelfinger, E.D., Hetz, C.,... Leyton, L. (2012). Astrocytic α vβ 3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering thy-1. PLoS ONE, 7(3). https://doi.org/10.1371/journal.pone.0034295

MLA:

Herrera-Molina, Rodrigo, et al. "Astrocytic α vβ 3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering thy-1." PLoS ONE 7.3 (2012).

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