Developmentally regulated activity of CRM1/XPO1 during early Xenopus embryogenesis.
In this work, we have investigated the role of CRM1/XPO1, a protein involved in specific export of proteins and RNA from the nucleus, in early Xenopus embryogenesis. The cloning of the Xenopus laevis CRM1, XCRM1, revealed remarkable conservation of the protein during evolution (96.7% amino acid identity between Xenopus and human). The protein and mRNA are maternally expressed and are present during early embryogenesis. However, our data show that the activity of the protein is developmentally regulated. Embryonic development is insensitive to leptomycin B, a specific inhibitor of CRM1, until the neurula stage. Moreover, the nuclear localization of CRM1 changes concomitantly with the appearance of the leptomycin B sensitivity. These data suggest that CRM1, present initially in an inactive form, becomes functional before the initiation of the neurula stage during gastrula-neurula transition, a period known to correspond to a critical transition in the pattern of gene expression. Finally, we confirmed the gastrula-neurula transition-dependent activation of CRM1 by pull-down experiments as well as by the study of the intracellular localization of a green fluorescent protein tagged with a nuclear export signal motif during early development. This work showed that the regulated activity of CRM1 controls specific transitions during normal development and thus might be a key regulator of early embryogenesis.
Callanan
M
M
Laboratoire de Biologie Moléculaire et Cellulaire de la Différenciation, INSERM U309, France.
Kudo
N
N
Gout
S
S
Brocard
M
M
Yoshida
M
M
Dimitrov
S
S
Khochbin
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D004351:Drug Resistance; D004625:Embryo, Nonmammalian / Q000378:metabolism; D019143:Evolution, Molecular; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005775:Gastrula / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D017403:In Situ Hybridization; D028884:Karyopherins; D008845:Microinjections; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014982:Xenopus laevis / Q000196:embryology*; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D000097606:Exportin 1 Protein; C038753:leptomycin B