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Comment
. 2012 Feb;233(2):740-4.
doi: 10.1016/j.expneurol.2011.11.016. Epub 2011 Nov 19.

Dendritic spine plasticity as an underlying mechanism of neuropathic pain: commentary on Tan et al

Ohannes K Melemedjian  1 , Theodore J Price
Affiliations
Comment

Dendritic spine plasticity as an underlying mechanism of neuropathic pain: commentary on Tan et al

Ohannes K Melemedjian et al. Exp Neurol. 2012 Feb.
No abstract available

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Figures

Fig. 1
Fig. 1
A) BDNF signals through the TrkB receptor to activate PI3K. PI3K in turn mediates the conversion of PIP2 to PIP3, both PI3K and PDK1 accumulate at the leading tip of growing protrusions that would differentiate into a dendritic spine. PIP3 recruits the polarity protein PARs which can activate Tiam, leading to the activation of Rac1. This allows for a localized activation of Rac1 and prevents its inappropriate activation. aPKCs function in a complex which include PARs and Rac1. The activity of aPKCs is dependent on Rac1 and PI3K-PDK1. Rac1 activates PAK which in turn activates LIMK. ADF/cofilin, a key regulator of actin polymerization, is phosphorylated by LIMK and dephosphorylated by PP2A. FMRP represses the function of PI3K and recruits PP2A mRNA. B) Systematic spatially and temporally regulated activation of various pathway leads to the sculpting of mushroom-shaped dendritic spines. ADF/cofilin activation and inactivation at the tip of a growing spine depolymerizes actin, which in concert with other pathways allows for the formation of mushroom shaped spine (wild type). Genetic loss of LIMK, which causes Williams Syndrome, leads to excessive ADF/cofilin activation due to dephosphorylation leading to increased depolymerization of actin and production of “stubby” spines (LIMK KO). Loss of FMRP function causes Fragile X Syndrome which leads to increased PI3K activity and ADF/cofilin inactivation, causes increased polymerization of actin and long dendritic spines. Loss of FMRP may also prevent the localized expression of PP2A leading to dysregulation in local ADF/cofilin activation and actin depolymerization (FMRP KO).
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