Show simple item record

Mechanisms of neurite outgrowth inhibition by Myelin-associated glycoprotein

dc.creatorPerdigoto, Ana Luisa Jordao
dc.date.accessioned2020-08-23T16:03:27Z
dc.date.available2010-12-22
dc.date.issued2010-12-22
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-12022010-212158
dc.identifier.urihttp://hdl.handle.net/1803/15014
dc.description.abstractAxonal regeneration in the central nervous system is prevented, in part, by inhibitory proteins expressed by myelin, including Myelin-associated glycoprotein (MAG). Although injury to the corticospinal tract can result in permanent disability, little is known regarding the mechanisms by which MAG affects cortical neurons. Here, we demonstrate that cortical neurons plated on MAG expressing CHO cells, exhibit a striking reduction in process outgrowth. Interestingly, none of the receptors previously implicated in MAG signaling, including the p75 neurotrophin receptor or gangliosides, contributed significantly to MAG-mediated inhibition. However, blocking the small GTPase Rho or its downstream effector kinase, ROCK, partially reversed the effects of MAG on the neurons. In addition, we identified the lipid phosphatase PTEN as a mediator of MAG’s inhibitory effects on neurite outgrowth. Knockdown or gene deletion of PTEN or over expression of activated AKT in cortical neurons resulted in significant, although partial, rescue of neurite outgrowth on MAG-CHO cells. PTEN knockout and Rho inactivation resulted in an additive effect on reversal of neurite outgrowth inhibition by MAG, suggesting that both molecules contribute to inhibition of cortical neurite outgrowth by MAG. Moreover, MAG decreased the levels of phospho-Akt, suggesting that it activates PTEN in the neurons. Taken together, these results suggest a novel pathway activated by MAG in cortical neurons involving the PTEN/PI3K/AKT axis.
dc.format.mimetypeapplication/pdf
dc.subjectcortical neurons
dc.subjectPTEN
dc.subjectMyelin-associated glycoprotein
dc.subjectneurite outgrowth
dc.subjectAKT
dc.titleMechanisms of neurite outgrowth inhibition by Myelin-associated glycoprotein
dc.typedissertation
dc.contributor.committeeMembergraham carpenter
dc.contributor.committeeMemberscott heibert
dc.contributor.committeeMemberJennifer Pietenpol
dc.contributor.committeeMemberDonna Webb
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplineBiochemistry
thesis.degree.grantorVanderbilt University
local.embargo.terms2010-12-22
local.embargo.lift2010-12-22
dc.contributor.committeeChairBruce Carter


Files in this item

Icon

This item appears in the following Collection(s)

Show simple item record