Search PubMed⌕ Search

Biomedical subjects

Ilan Davis

Publications and source records attributed to Ilan Davis.

7 recordsLinked to original sources

Dynein anchors its mRNA cargo after apical transport in the Drosophila blastoderm embryo.

Molecular motors actively transport many types of cargo along the cytoskeleton in a wide range of organisms. One class of cargo is localized mRNAs, which are transported by myosin on actin filaments or by kinesin and dynein on microtubules. How the cargo is kept at its final intracellular destination and whether the motors are recycled after completion of transport are poorly understood. Here, we use a new RNA anchoring assay in living Drosophila blastoderm embryos to show that apical anchoring of mRNA after completion of dynein transport does not depend on actin or on continuous active transport by the motor. Instead, apical anchoring of RNA requires microtubules and involves dynein as a static anchor that remains with the cargo at its final destination. We propose a general principle that could also apply to other dynein cargo and to some other molecular motors, whereby cargo transport and anchoring reside in the same molecule.

Animals↗

gurken and the I factor retrotransposon RNAs share common localization signals and machinery.

Drosophila gurken mRNA is localized by dynein-mediated transport to a crescent near the oocyte nucleus, thus targeting the TGFalpha signal and forming the primary embryonic axes. Here, we show that gurken and the I factor, a non-LTR retrotransposon, share a small consensus RNA stem loop of defined secondary structure, which forms a conserved signal for dynein-mediated RNA transport to the oocyte nucleus. Furthermore, gurken and the I factor compete in vivo for the same localization machinery. I factor transposition leads to its mRNA accumulating near and within the oocyte nucleus, thus causing perturbations in gurken and bicoid mRNA localization and axis specification. These observations further our understanding of the close association of transposable elements with their host and provide an explanation for how I factor transposition causes female sterility. We propose that the transposition of other elements may exploit the host's RNA transport signals and machinery.

Animals↗

mRNA localisation gets more complex.

Recent advances in techniques for visualising mRNA movement in living cells have led to rapid progress in understanding the mechanism of mRNA localisation in the cytoplasm. There is an emerging consensus that in many cases the mRNA signals that determine intracellular destination are more complex and difficult to define than was first anticipated. Furthermore, the transacting factors that interpret the mRNA signals are numerous and their combinations change during the life of an mRNA, perhaps allowing the selection of many sub-destinations in the cell. Lastly, an emerging theme over the past few years is that many proteins that determine the destinations of mRNAs are recruited on nascent transcripts in the nucleus. They often function in many different processes in the biogenesis of mRNA and probably act in concert to provide specificity.

Animals↗

Drosophila gurken (TGFalpha) mRNA localizes as particles that move within the oocyte in two dynein-dependent steps.

In Drosophila oocytes, gurken mRNA localization orientates the TGF-alpha signal to establish the anteroposterior and dorsoventral axes. We have elucidated the path and mechanism of gurken mRNA localization by time-lapse cinematography of injected fluorescent transcripts in living oocytes. gurken RNA assembles into particles that move in two distinct steps, both requiring microtubules and cytoplasmic Dynein. gurken particles first move toward the anterior and then turn and move dorsally toward the oocyte nucleus. We present evidence suggesting that the two steps of gurken RNA transport occur on distinct arrays of microtubules. Such distinct microtubule networks could provide a general mechanism for one motor to transport different cargos to distinct subcellular destinations.

Animals↗

Dcas is required for importin-alpha3 nuclear export and mechano-sensory organ cell fate specification in Drosophila.

We have studied the in vivo function and tissue specificity of Dcas, the Drosophila ortholog of CAS, the importin beta-like export receptor for importin alpha. While dcas mRNA is specifically expressed in the embryonic central nervous system, Dcas protein is maternally supplied to all embryonic cells and its nuclear/cytoplasmic distribution varies in different tissues and times in development. Unexpectedly, hypomorphic alleles of dcas show specific transformations in mechano-sensory organ cell identity, characteristic of mutations that increase Notch signaling. Dcas is essential for efficient importin-alpha3 nuclear export in mechano-sensory cells and the surrounding epidermal cells and is indirectly required for the import of one component of the Notch pathway, but not others tested. We interpret the specificity of the dcas phenotype as indicating that one or more Notch signaling components are particularly sensitive to a disruption in nuclear protein import. We propose that mutations in house keeping genes often cause specific developmental phenotypes, such as those observed in many human genetic disorders.

Active Transport, Cell Nucleus↗

Intracellular mRNA localization: motors move messages.

Intracellular mRNA localization is a common mechanism of post-transcriptional regulation of gene expression. In a wide range of organisms, mRNA localization coupled with translational regulation target the proteins to their site of function. Here, we describe recent exciting evidence that some mRNAs are transported as particles along the cytoskeleton by the molecular motors dynein, kinesin or myosin. We discuss the key questions of how localized mRNAs might be linked to motors and what determines their cytoplasmic destinations.

Animals↗