Disease relevance of sn

• In their mutational properties, the sn mutants are analogous to insertion sequence (IS) elements and bacteriophage Mu of Escherichia coli, but the precise nature of the insertion remains unknown [1].

High impact information on sn

• Using cross-linker-specific antibodies, mutants, and drugs we show that fascin and actin are present in excessive amounts throughout bundle elongation [2].
• Specifically, inhibition of phosphorylation by staurosporine results in a failure to form large bundles if added during bundle formation, and leads to a loss of cross-linking by fascin if added after the bundles form [2].
• By extracting fully elongated bristles with potassium iodide which removes fascin but leaves forked, the bundles change from being straight to twisted and the filaments within them become poorly ordered [3].
• Fascin is found in actin filament bundles in microvilli of sea urchin eggs and in filopodial extensions in coelomocytes [4].
• Drosophila singed, a fascin homolog, is required for actin bundle formation during oogenesis and bristle extension [4].

Biological context of sn

• Phenotypes of Drosophila brain neurons in primary culture reveal a role for fascin in neurite shape and trajectory [5].
• This is the first demonstration of fascin function in neuronal morphogenesis [5].
• A series of eleven independent mutants at the X chromosome singed bristle (sn) locus of Drosophila melanogaster is described [1].

Anatomical context of sn

• Fascin deficiency does not impair the 20E response, but neurites fail to maintain their normal, nearly straight trajectory, instead forming curls and hooks [5].

Associations of sn with chemical compounds

• The induction of visible mutations by MR is observed at only a limited number of genes, such as singed bristle (sn), raspberry eye colour (ras), yellow body colour (y) and a carmine eye colour (car) [6].
• A mutation that changes glycine 409 to glutamic acid results in partial inactivation of fascin in vivo; singedG409E mutants have kinked bristles and are fertile with a mild nurse cell cytoplasm transport defect [7].
• A mutation that changes serine 289 to asparagine almost completely inactivates fascin in vivo; singedS289N mutants have gnarled bristles and are sterile due to a severe defect in nurse cell cytoplasm transport caused by the absence of nurse cell cytoplasmic actin bundles [7].

Other interactions of sn

• From these observations we conclude that (a) forked is used early in development to aggregate the tiny bundles into larger bundles; and (b) forked facilitates fascin entry into the bundles to maximally cross-link the actin filaments into straight, compact, rigid bundles [3].
• In nurse cells that contain excess quail but no fascin, the cytoplasmic actin network initially appears wild type but then becomes disorganized in the final stages of nurse cell cytoplasm transport [8].
• Drosophila fascin mutants are rescued by overexpression of the villin-like protein, quail [8].
• Furthermore, as pimples and microvilli form in the absence of both forked and fascin crossbridges, we also conclude that neither of these crossbridges account for core bundle formation in microvilli, but there must exist a third, as yet unidentified crossbridge in this system [9].

References