Dicty News Electronic Edition Volume 25, number 5 September 2, 2005 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of Dicty-News, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. ============= Abstracts ============= Paxillin is required for cell-substrate adhesion, cell sorting and slug migration during Dictyostelium development Tanya Bukahrova, Gertrud Weijer, Leonard Bosgraaf, Dirk Dormann, Peter J. van Haastert, Cornelis J Weijer Journal of Cell Science, in press Paxillin is a key regulatory component of focal adhesion sites, implicated in controlling cell-substrate interactions and cell movement. We analyse the function of a Dictyostelium discoideum paxillin homologue, PaxB, which contains 4 highly conserved LD and 4 LIM domains, but lacks two characteristic tyrosine residues, that form the core of vertebrate SH2 binding domains. PaxB is expressed during growth and all stages of development, but expression peaks during slug formation. Using a paxB-gfp knockin strain we show the existence of focal adhesions and characterise their dynamics. During multicellular development PaxB is not only found in focal adhesions at the cell-substrate interface, but also in the tips of filopodial structures predominantly located at the trailing ends of cells. paxB- strains are less adhesive to the substrate, they can aggregate but multicellular development from the mound stage onwards is severely impeded. paxB- strains are defective in proper celltype proportioning, cell sorting, slug migration and form defective fruiting bodies. Mutation of a conserved JNK phosphorylation site, implicated in the control of cell migration, does not have any major effects on cell sorting, slug migration or morphogenesis in Dictyostelium. PaxB does not appear to function redundantly with its closest relative Lim2 (paxA), which when deleted also results in a mound arrest phenotype. However analysis of paxA- and paxB- single and double null mutants suggest that PaxB may act upstream of Lim2. Submitted by: Kees Weijer [c.j.weijer@dundee.ac.uk] ----------------------------------------------------------------------------- Isolation and synthesis of a new aromatic compound, brefelamide, from Dictyostelium cellular slime molds and its inhibitory effect on proliferation of astrocytoma cells. Kikuchi H, Saito Y, Sekiya J, Okano Y, Saito M, Nakahata H, Kubohara Y & Oshima, Y. Graduate School of Phamaceutical Sciences, Tohoku Univiersity, Japan. etc. J. Org. Chem., In press. We have explored the diversity of secondary metabolites produced by cellular slime molds to examine the possible use of such cellular slime molds as a resource for novel drug development. A new aromatic amide, brefelamide, was isolated from methanol extracts of the fruiting bodies of Dictyostelium brefeldianum and D. giganteum. The structure of brefelamide was determined by spectral means including EIMS and 1H and 13C NMR. The total synthesis of brefelamide was carried out to confirm the structure and obtain sufficient samples for performing biological evaluation. Interestingly, the compound inhibited the cellular proliferation of 1321N1 human astrocytoma cells. Submitted by: Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp] ============================================================================== [End Dicty News, volume 25, number 5]