Specification of Organ size and shape during development.
Elaborate network of signalling pathways ensure growth control during animal development such that various organs and tissues attain specific size and shape. Disturbance in any component of this intricate growth control mechanism in human would result in cancer and many ageing-related disorders. I will discuss our efforts in identifying key regulators of growth during epithelial tissue morphogenesis using the fruitfly, Drosophila melanogaster. Human orthologues of many of those players are implicated in aggressive tumors and metastasis.
Sendai Virus Recruits Cellular Villin to Remodel Actin Cytoskeleton During Fusion with Hepatocytes: Implications in Liver Gene Therapy
Reconstituted Sendai viral envelopes (Virosomes) are well recognized for their promising potential in membrane fusion mediated delivery of bioactive molecules to liver cells. Despite the known function of viral envelope glycoproteins in catalyzing fusion with the cellular membrane, the role of host cell proteins remains elusive. Here, we used two-dimensional differential in-gel electrophoresis (2D-DIGE) to analyze hepatic cells in early response to virosome-induced membrane fusion. Quantitative mass spectrometry together with biochemical analysis revealed that villin, an actin-modifying protein, is differentially up-regulated and phosphorylated at Threonine-206 (T206), as an early molecular event during membrane fusion. We found that villin influences actin dynamics which, in turn, promotes membrane mixing through an active participation of Sendai viral envelope glycoproteins. Modulation of villin in host cells also resulted in a discernible effect on the entry and egress of progeny Sendai virus. Taken together, these results suggest a novel mechanism of regulated viral entry in animal cells mediated by host factor villin.