Although axonal protein synthesis has been clearly documented during development

and regeneration (Andreassi et al., 2010 and Lin and Holt, 2008) and a large number of mRNAs have been detected in growth cones (Zivraj et al., 2010), it remains unclear selleck chemicals whether mature axons of the CNS are capable of local protein synthesis. Here, we demonstrate mRNAs coding for proteins associated with presynaptic function are present in the mature rat neuropil, suggesting the possibility that healthy adult axons are the sites of protein synthesis. We also detected the mRNAs for many membrane proteins, including a large number of voltage-gated ion channels: 5 distinct Na+, 15 Ca2+, and 33 K+ channel subunits (Table S10). It is known that many of these channels are expressed in gradients from the soma to the dendrites, resulting in local control of signaling as well as the excitability of the dendrites (Johnston and Narayanan, 2008 and Makara et al., 2009). For example, synaptic excitation has been shown to suppress translation of Kv1.1 (Raab-Graham et al., 2006), resulting in enhanced excitability of pyramidal neurons. The presence of multiple K+, Ca2+, and Na+ channel subunits mRNAs in our dendritic/axonal data set suggests that local translation

could establish, maintain, and regulate CP-673451 order these protein gradients, resulting in local control of the dendritic integrative properties. If membrane protein mRNAs are translated locally then the machinery required for co- and posttranslational processing of these proteins should also be localized. While it is clear that

there are some components of ER and Golgi present (Gardiol et al., 1999, Horton and Ehlers, 2003, Horton et al., 2005 and Torre and Steward, 1996), it remains a matter of debate as to the nature and location of membrane protein processing. It is thus interesting that we identified mRNAs for components of the secretory pathway as well as many enzymes associated with the N-glycosylation pathway including secondly key enzymes that influence ER export and complex type N-glycan biosynthesis. The glycosylation status of a membrane protein influences its folding, trafficking, as well as membrane residence time and function. The detection of mRNAs for membrane proteins as well as secretory pathway components and enzymes strengthen the view that membrane protein synthesis and processing might occur locally (Gardiol et al., 1999 and Torre and Steward, 1996) (Table S11). Local translation has been implicated in neurodevelopmental, psychiatric or degenerative diseases (Swanger and Bassell, 2011).