AP2 Regulates Thickveins Trafficking to Attenuate NMJ Growth Signaling in Drosophila.

Compromised endocytosis in neurons leads to synapse overgrowth and altered organization of synaptic proteins. However, the molecular players and the signaling pathways which regulate the process remain poorly understood. Here, we show that σ2-adaptin, one of the subunits of the AP2-complex, genetically interacts with Mad, Medea and Dad (components of BMP signaling) to control neuromuscular junction (NMJ) growth in Drosophila Ultrastructural analysis of σ2-adaptin mutants show an accumulation of large vesicles and membranous structures akin to endosomes at the synapse. We found that mutations in σ2-adaptin lead to an accumulation of Tkv receptors at the presynaptic membrane. Interestingly, the level of small GTPase Rab11 was significantly reduced in the σ2-adaptin mutant synapses. However, expression of Rab11 does not restore the synaptic defects of σ2-adaptin mutations. We propose a model in which AP2 regulates Tkv internalization and endosomal recycling to control synaptic growth.

RdgB proteins: functions in lipid homeostasis and signal transduction.

The RdgBs are a group of evolutionarily conserved molecules that contain a phosphatidylinositol transfer protein (PITP) domain. However in contrast to classical PITPs (PITPalpha) with whom they share the conserved PITP domain, these proteins also contain several additional sequence elements whose functional significance remains unknown. The founding member of the family DrdgB alpha (Drosophila rdgB) appears to be essential for sensory transduction and maintenance of ultra structure in photoreceptors (retinal sensory neurons). Although proposed to support the maintenance of phosphatidylinositol 4, 5 bisphosphate [PI (4, 5) P(2)] levels during G-protein coupled phospholipase C activity in these cells, the biochemical mechanism of DrdgB alpha function remains unresolved. More recently, a mammalian RdgB protein has been implicated in the maintenance of diacylglycerol (DAG) levels and secretory function at Golgi membranes. In this review we discuss existing work on the function of RdgB proteins and set out future challenges in understanding this group of lipid transfer proteins.

Mutants in Drosophila TRPC channels reduce olfactory sensitivity to carbon dioxide.

BACKGROUND: Members of the canonical Transient Receptor Potential (TRPC) class of cationic channels function downstream of Gαq and PLCß in Drosophila photoreceptors for transducing visual stimuli. Gαq has recently been implicated in olfactory sensing of carbon dioxide (CO(2)) and other odorants. Here we investigated the role of PLCß and TRPC channels for sensing CO(2) in Drosophila. METHODOLOGY/PRINCIPAL FINDINGS: Through behavioral assays it was demonstrated that Drosophila mutants for plc21c, trp and trpl have a reduced sensitivity for CO(2). Immuno-histochemical staining for TRP, TRPL and TRPγ indicates that all three channels are expressed in Drosophila antennae including the sensory neurons that express CO(2) receptors. Electrophysiological recordings obtained from the antennae of protein null alleles of TRP (trp(343)) and TRPL (trpl(302)), showed that the sensory response to multiple concentrations of CO(2) was reduced. However, trpl(302); trp(343) double mutants still have a residual response to CO(2). Down-regulation of TRPC channels specifically in CO(2) sensing olfactory neurons reduced the response to CO(2) and this reduction was obtained even upon down-regulation of the TRPCs in adult olfactory sensory neurons. Thus the reduced response to CO(2) obtained from the antennae of TRPC RNAi strains is not due to a developmental defect. CONCLUSION: These observations show that reduction in TRPC channel function significantly reduces the sensitivity of the olfactory response to CO(2) concentrations of 5% or less in adult Drosophila. It is possible that the CO(2) receptors Gr63a and Gr21a activate the TRPC channels through Gαq and PLC21C.