dFMRP and Caprin, translational regulators of synaptic plasticity, control the cell cycle at the Drosophila mid-blastula transition.
The molecular mechanisms driving the conserved metazoan developmental shift referred to as the mid-blastula transition (MBT) remain mysterious. Typically, cleavage divisions give way to longer asynchronous cell cycles with the acquisition of a gap phase. In Drosophila, rapid synchronous nuclear divisions must pause at the MBT to allow the formation of a cellular blastoderm through a special form of cytokinesis termed cellularization. Drosophila Fragile X mental retardation protein (dFMRP; FMR1), a transcript-specific translational regulator, is required for cellularization. The role of FMRP has been most extensively studied in the nervous system because the loss of FMRP activity in neurons causes the misexpression of specific mRNAs required for synaptic plasticity, resulting in mental retardation and autism in humans. Here, we show that in the early embryo dFMRP associates specifically with Caprin, another transcript-specific translational regulator implicated in synaptic plasticity, and with eIF4G, a key regulator of translational initiation. dFMRP and Caprin collaborate to control the cell cycle at the MBT by directly mediating the normal repression of maternal Cyclin B mRNA and the activation of zygotic frühstart mRNA. These findings identify two new targets of dFMRP regulation and implicate conserved translational regulatory mechanisms in processes as diverse as learning, memory and early embryonic development.
The Section of MCD Biology and Institute for Cellular and Molecular Biology, The University of Texas at Austin, TX 78712, USA. papoulas@mail.utexas.edu
Ophelia
O
Papoulas
Kathryn F
KF
Monzo
Greg T
GT
Cantin
Cristian
C
Ruse
John R
JR
Yates
Young Hee
YH
Ryu
John C
JC
Sisson
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D019926:Cyclin B / Q000235:genetics; D004330:Drosophila / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D039603:Eukaryotic Initiation Factor-4G / Q000235:genetics / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D011485:Protein Binding
D018797:Cell Cycle Proteins; D019926:Cyclin B; D029721:Drosophila Proteins; D039603:Eukaryotic Initiation Factor-4G; D051860:Fragile X Messenger Ribonucleoprotein 1; C477649:Z600 protein, Drosophila; C523051:eIF4G2 protein, Drosophila