A forward genetic screen in Drosophila melanogaster to identify mutations affecting INAD localization in photoreceptor cells.

In Drosophila photoreceptors, the multivalent PDZ protein INAD interacts with multiple signaling components and localizes complexes to the rhabdomere, a subcellular compartment specialized for phototransduction. Since this localization is critical for signaling, we conducted a genetic screen of the third chromosome for mutations that result in mislocalization of an INAD-GFP fusion protein. We identified seven mutant lines that fall into two complementation groups, idl (INAD localization)-A and idl-B.

Cell-nonautonomous function of ceramidase in photoreceptor homeostasis.

Neutral ceramidase, a key enzyme of sphingolipid metabolism, hydrolyzes ceramide to sphingosine. These sphingolipids are critical structural components of cell membranes and act as second messengers in diverse signal transduction cascades. Here, we have isolated and characterized functional null mutants of Drosophila ceramidase.

DLGS97/SAP97 is developmentally upregulated and is required for complex adult behaviors and synapse morphology and function.

The synaptic membrane-associated guanylate kinase (MAGUK) scaffolding protein family is thought to play key roles in synapse assembly and synaptic plasticity. Evidence supporting these roles in vivo is scarce, as a consequence of gene redundancy in mammals. The genome of Drosophila contains only one MAGUK gene, discs large (dlg), from which two major proteins originate: DLGA [PSD95 (postsynaptic density 95)-like] and DLGS97 [SAP97 (synapse-associated protein)-like].

Light-induced recruitment of INAD-signaling complexes to detergent-resistant lipid rafts in Drosophila photoreceptors.

Here, we reveal a novel feature of the dynamic organization of signaling components in Drosophila photoreceptors. We show that the multi-PDZ protein INAD and its target proteins undergo light-induced recruitment to detergent-resistant membrane (DRM) rafts. Reduction of ergosterol, considered to be a key component of lipid rafts in Drosophila, resulted in a loss of INAD-signaling complexes associated with DRM fractions.