Outsourcing CREB translation to axons to survive

Abstract

Nerve growth factor induces sensory neuron survival via retrograde signalling from the axon to the cell body. Local translation of the transcription factor CREB in the axon, followed by its transport to the nucleus, is involved in this process.

Figure 1

Compartmentalized cultures reveal axonal synthesis and retrograde transport of CREB. (a) Schematic representations of compartmentalized culture systems. Experimental treatments can be applied exclusively to cell bodies or axons using a Campenot chamber, in which neurons plated in the cell body compartment extend axons through a fluidically sealed barrier to an axonal compartment isolated from the cell bodies (left). RNA and proteins can be isolated exclusively from cell bodies or axons using a modified Boyden chamber, in which DRG explants are plated on one side of a microporous membrane and axons grow through to the other side (pore diameter permits only passage of axons), allowing cell bodies or axons to be removed separately by scraping (right). (B) Schematic representation of a model for axonal synthesis and retrograde transport of CREB. (a) Activated TrkA receptor undergoes endocytosis and activates local synthesis of CREB through an unknown mechanism. (b) Locally synthesized CREB is transported to the cell body along microtubules in a complex with the NGF–pTrkA signalling endosome. (c) At the cell body, axonally synthesized CREB is most likely the source of nuclear pCREB, possibly because axonal CREB, but not cell-body CREB, is in close enough proximity to the signalling endosome to be efficiently phosphorylated (adapted from Cox et al.).