Mnk is a negative regulator of cap-dependent translation in Aplysia neurons.
To investigate the mechanisms underlying regulation of eukaryotic initiation factor 4E (eIF4E) phosphorylation in Aplysia neurons, we have cloned the Aplysia homolog of the vertebrate eIF4E kinases, Mnk1 and -2. Aplysia Mnk shares many conserved regions with vertebrate Mnk, including putative eukaryotic initiation factor 4G binding regions, activation loop phosphorylation sites, and a carboxy-terminal anchoring site for MAP kinases. As expected, purified Aplysia Mnk phosphorylated Aplysia eIF4E at a conserved carboxy-terminal serine and over-expression of Aplysia Mnk in sensory neurons led to increased phosphorylation of endogenous eIF4E. Over-expression of Aplysia Mnk led to strong decreases in cap-dependent translation, while generally sparing internal ribosomal entry site (IRES)-dependent translation. However, decreases in cap-dependent translation seen after expression of Aplysia Mnk could only be partly explained by increases in eIF4E phosphorylation. In Aplysia sensory neurons, phosphorylation of eIF4E is reduced during intermediate memory formation. However, we found that this physiological regulation of eIF4E phosphorylation was independent of changes in Aplysia Mnk phosphorylation. We propose that changes in eIF4E phosphorylation in Aplysia neurons are a consequence of changes in cap-dependent translation that are independent of regulation of Aplysia Mnk.
Ross
Gabriel
G
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Dyer
John R
JR
Castellucci
Vincent F
VF
Sossin
Wayne S
WS
D000818:Animals; D001048:Aplysia / Q000166:cytology / Q000201:enzymology*; D001665:Binding Sites / Q000502:physiology; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D008969:Molecular Sequence Data; D009420:Nervous System / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology*; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; D014157:Transcription Factors; C106281:Mknk1 protein, mouse; C106282:Mknk2 protein, mouse; D017346:Protein Serine-Threonine Kinases