Subsequent studies confirmed this result in different DNA Damage inhibitor neurons (Wu et al., 2005 and Yao et al., 2006) and revealed that local protein synthesis underlies growth-cone adaptation, gradient sensing, and directional turning
in growing axons (Leung et al., 2006, Ming et al., 2002, Piper et al., 2005 and Yao et al., 2006). In addition, axonal protein synthesis is elicited in response to injury and plays key roles in axon regeneration and maintenance (Jung et al., 2012, Perry et al., 2012, Verma et al., 2005, Yoon et al., 2012 and Zheng et al., 2001). Neuronal function is highly dependent on spatially precise signaling. Increasing evidence indicates that the complex morphology of neurons has created biological compartments that subdivide the neuron into spatially distinct signaling domains important for neuronal function LY294002 in vitro (Hanus and Schuman, 2013). Dendritic spines represent a specialized (“classical”) cellular compartment in which subsets of specific proteins (e.g. receptors, channels, signaling molecules, and scaffolds) are collected together with a common function for receiving and processing electrical and chemical input. Spines have a
distinct structural morphology and, as such, are easy to classify as a compartment. Although spines are small (∼1 μm3), they can still be subdivided into further functional compartments (see Chen and Sabatini, 2012 for review) with multiple microdomains, raising the question of how a compartment is defined. next For example, a recent superresolution imaging study demonstrated that, within synapses, AMPA receptors are clustered into small nanodomains (∼70 nm in diameter) that contain on average ∼20 receptors (Nair et al., 2013). These nanodomains are dynamic in both their shape and position and may have a limited lifetime. Anatomically and functionally distinct compartments also exist in axons, such as the growth cone, the axon initial segment, and terminal arbor. Equally, there are examples
of compartments that exhibit no obvious “anatomical” specializations. In axons, for example, some membrane proteins are localized to restricted segments of the axon (Fasciclins, Tag1/L1, Robo) (Bastiani et al., 1987, Dodd et al., 1988, Katsuki et al., 2009 and Rajagopalan et al., 2000) indicative of plasma-membrane compartmentalization. In addition, second-messenger signaling molecules such as calcium and cyclic nucleotides, once thought to signal extensively throughout a cell, are now known to be highly regulated such that increases in concentration can be confined to a small space, creating a signaling compartment. Selective activation of a single spine on a dendrite, for example, can provide the receiving neuron with information about a specific stimulus (Varga et al., 2011).