Local protein synthesis and spine morphogenesis: Fragile X syndrome and beyond

Abstract

Behavioral experiences can modulate neural networks through changes in synaptic morphology and number. In contrast, abnormal morphogenesis of dendritic spines is associated with cognitive impairment, as in Fragile X syndrome. Dendritic or synaptic protein synthesis could provide the specificity and speed necessary for spine morphogenesis. Here, we highlight locally translated proteins shown to affect synaptic morphology (e.g., Fragile X mental retardation protein).

Figure 1.

Synaptic stimulation can act via ionotropic glutamate receptors (AMPA/NMDA; 1a) and mGluRs (1b) and can initiate translation (2) of locally synthesized proteins (3; shown in yellow), including regulators (underlined red text) and plastic structural elements (black text). Both broad categories of proteins can interact with a Rho GTPase pathway (4; simplified here for illustration purposes), affecting morphology through rearrangement of actin filaments (5). Locally synthesized proteins can thereby interact to assemble or reorganize the spine, regulating function and affecting future spine morphogenesis (see text for details). NMDAR, NMDA receptor; AMPAR, AMPA receptor; PAK, α-p-21-activated kinase; LIMK, LIM-kinase; IP₃R, IP₃ receptor; sER, smooth endoplasmic reticulum.