Ultimately, a neuron must integrate the information received

from multiple compartments. As such, future experiments aimed at understanding how different compartments emerge and what mechanisms generate such spatially precise intracellular patterning will be very informative. Selleckchem Volasertib Compartmentalized signaling presents several challenges to the cell, a prime one being the localization of its component parts. Specific molecules must be transported and delivered to the appropriate subcellular destinations. One of the remarkable features of RNA is its ability to be spatially localized and, therefore, potentially contribute to neuronal compartmentalization. Historically, localized mRNAs have been studied during development (see Martin and Ephrussi, 2009). That localized RNA is more often the rule than the exception is spectacularly illustrated by the finding that 71% of the Drosophila embryo transcriptome is localized to specific subcellular compartments ( Lécuyer et al., 2007). The proteins encoded by localized mRNAs are also concentrated at the site suggesting that mRNA localization and the ensuing local translation

plays an important role in positioning proteins for cellular functions. A general function of mRNA localization is the generation of asymmetry. mRNAs tend to be abundantly localized to the peripheral domains and motile parts of neurons where they are optimally positioned for the arrival of external signals, e.g., in dendrites (synaptic activation) DNA Damage inhibitor and growth cones. Subcellular

asymmetry can lead to highly polarized dynamics and cell morphology that can operate on a remarkably fine scale. To navigate, growth cones must be able to make directional turns, which demands asymmetry. In retinal growth cones, for example, which are only 5 μm in diameter, a polarized external Edoxaban gradient of netrin-1 triggers increases in both the transport and translation of β-actin mRNA on the gradient near side (Leung et al., 2006 and Yao et al., 2006). This polarized translation leads to a rapid (5 min) polarized increase in β-actin protein that helps to drive axon turning towards the gradient source. Interestingly, different cues show specificity in their effects on mRNA transport and translation. Different growth factors, for example, trigger the transport of a specific repertoire of mRNAs in axons (Willis et al., 2005, Willis et al., 2007 and Zhang et al., 1999), and different guidance cues elicit the translation of specific subsets of mRNAs (Leung et al., 2006, Piper et al., 2006, Shigeoka et al., 2013, Wu et al., 2005 and Yao et al., 2006). β-actin mRNA translation is triggered by netrin-1 but not Sema3A, whereas RhoA and cofilin mRNA translation is induced by Sema3A but not netrin-1.