, 2008). In other words, there are signal-sequence-independent mechanisms that direct mRNA localizations to the ER. Since the ER permeates the entire neuron including the axonal processes, some mRNAs could be simply carried by the ER into axons (Figure 1B). Accumulating evidence has shown

that axons of nonmammalian neurons and embryonic mammalian neurons have the capacity to synthesize proteins, and in vivo in the adult mouse, ribosomes could be transferred Autophagy Compound Library from Schwann cells to the injured distal axons of the peripheral nerve (Twiss and Fainzilber, 2009, and the references therein). Nevertheless, ribosomes were rarely observed in axons of mature central nervous system neurons in mammals, although they could be found in the axon hillock (Steward, 1997). The cellular mechanisms that prevent ribosomes from entering into the axons of mature neurons remain unclear, although it is conceivable that in immature growing neurons, ribosomes may move into axons as part of the vectorial flow of cytoplasm (Bradke and Dotti, 1997). Perhaps as the neurons mature and become polarized, their axon initial segment (AIS) is established and the AIS serves as a selective cytoplasmic “filter” (Song et al., 2009) that excludes ribosomes from getting into axons. This possibility could, in principle, be examined in mature neurons in which the AIS is acutely disrupted Pazopanib by conditional deletion of the specific ankyrin

G isoform (Grubb and Burrone, 2010). Finally, it will also be interesting to examine whether this mechanism of integrating two major types of target-derived signals, i.e., neurotrophic factors stimulating the axonal synthesis only of SMADs and TGFβ-superfamily factors forming retrograde

signaling endosomes, is used elsewhere in the nervous system for retrograde specification of neuronal subtype identities. “
“The function of the nervous system relies on billions of neurons and their synapses. Loss of neurons and synapses is a feature of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases (Lin and Koleske, 2010). This feature can be replicated in mice lacking cysteine string protein α (CSPα) (Chandra et al., 2005 and Fernández-Chacón et al., 2004), a presynaptic vesicle protein that has been implicated in the pathogenesis of neurodegenerative diseases (Nosková et al., 2011). Knockout of CSPα causes activity-dependent synapse loss, progressive defects in neurotransmission, neurodegeneration, and early lethality in mice (Chandra et al., 2005 and Fernández-Chacón et al., 2004). CSPα KO is therefore a useful tool to study mechanisms underlying synapse loss and neurodegeneration. A thorough understanding on how CSPα works at synapses is a prerequisite to understand the mechanisms underlying synapse loss in CSPα KO mice. In this issue of Neuron, Zhang et al. (2012) and Rozas et al. (2012) found a new role of CSPα—regulation of synaptic vesicle endocytosis via interaction with the vesicle fission protein dynamin 1 ( Figure 1).