ABSTRACT
Extracellular signals regulate protein translation in many cell functions. A key advantage of control at the translational level is the opportunity to regulate protein synthesis within specific cellular subregions. However, little is known about mechanisms that may link extracellular cues to translation with spatial precision. Here, we show that a transmembrane receptor, DCC, forms a binding complex containing multiple translation components, including eukaryotic initiation factors, ribosomal large and small subunits, and monosomes. In neuronal axons and dendrites DCC colocalizes in particles with translation machinery, and newly synthesized protein. The extracellular ligand netrin promoted DCC-mediated translation and disassociation of translation components. The functional and physical association of a cell surface receptor with the translation machinery leads to a generalizable model for localization and extracellular regulation of protein synthesis, based on a transmembrane translation regulation complex.
Subject(s)
Neurons/metabolism , Protein Biosynthesis , Receptors, Cell Surface/metabolism , Ribosomal Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Amino Acid Motifs , Animals , Axons/metabolism , Cells, Cultured , Chick Embryo , Dendrites/metabolism , Hippocampus/cytology , Hippocampus/metabolism , Humans , Mice , Nerve Growth Factors/metabolism , Netrin-1 , Protein Structure, Tertiary , Rats , Receptors, Cell Surface/chemistry , Ribosomes/metabolism , Tumor Suppressor Proteins/chemistryABSTRACT
As axons grow past intermediate targets, they change their responsiveness to guidance cues. Local upregulation of receptor expression is involved, but the mechanisms for this are not clear. Here protein synthesis is traced within individual axons by introducing RNAs encoding visualizable reporters. Individual severed axons and growth cones can translate proteins and also export them to the cell surface. As axons reach the spinal cord midline, EphA2 is among the receptors upregulated on at least some distal axon segments. Midline reporter upregulation is recapitulated by part of the EphA2 mRNA 3' untranslated region, which is highly conserved and includes known translational control sequences. These results show axons contain all the machinery for protein translation and cell surface expression, and they reveal a potentially general and flexible RNA-based mechanism for regulation localized within a subregion of the axon.