mPER1-mediated nuclear export of mCRY1/2 is an important element in establishing circadian rhythm.
Receptor-mediated nucleocytoplasmic transport of clock proteins is an important, conserved element of the core mechanism for circadian rhythmicity. A systematic analysis of the nuclear export characteristics for the different murine period (mPER) and cryptochrome (mCRY) proteins using Xenopus oocytes as an experimental system demonstrates that all three mPER proteins, but neither mCRY1 nor mCRY2, are exported if injected individually. However, nuclear injection of heterodimeric complexes that contain combinations of mPER and mCRY proteins shows that mPER1 serves as an export adaptor for mCRY1 and mCRY2. Functional analysis of dominant-negative mPER1 variants designed either to sequester mPER3 to the cytoplasm or to inhibit nuclear export of mCRY1/2 in synchronized, stably transfected fibroblasts suggests that mPER1-mediated export of mCRY1/2 defines an important new element of the core clock machinery in vertebrates.
Loop
Susanne
S
Abteilung Entwicklungsbiochemie, Georg-August-Universität, Justus von Liebig Weg 11, 37077 Göttingen, Germany.
Katzer
Mathias
M
Pieler
Tomas
T
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D003001:Cloning, Molecular; D056931:Cryptochromes; D003593:Cytoplasm / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism*; D040461:Gene Components; D047468:Immunoprecipitation; D051379:Mice; D008845:Microinjections; D046912:Multiprotein Complexes / Q000096:biosynthesis; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes; D056950:Period Circadian Proteins; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029867:Xenopus Proteins; D014982:Xenopus laevis
D018797:Cell Cycle Proteins; D056931:Cryptochromes; D005420:Flavoproteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C539025:Per1 protein, Xenopus; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D029867:Xenopus Proteins