Phosphoinositides (PIs) have been implicated in neural and behavioral plasticity. In C. elegans, phosphatidylinositol 3, 4, 5-trisphosphate (PIP3) and diacylglycerol (DAG) signaling play pivotal roles in the plasticity of salt chemotaxis. Worms avoid NaCl after starvation in the presence of ordinarily chemoattractive NaCl, and this behavioral plasticity is called salt chemotaxis learning. Previous studies showed that PIP3 signaling in the ASER salt-sensing neuron promotes the learning, leading to avoidance of NaCl. In contrast, DAG signaling in ASER counteracts PIP3 signaling and promotes attraction behavior towards NaCl (Tomioka et al, 2006). However, remarkably little is known about the spatiotemporal dynamics of PI in neurons.In the present study, we screened for mutants defective in salt chemotaxis learning and identified a novel gene M01F1.7. Both alleles of M01F1.7,
pe1209 and
tm1500, show learning defects (i.e., they are attracted to NaCl even after training) as well as slightly but significantly reduced attraction to NaCl in naive animals. M01F1.7 is orthologous to mammalian Pitpnm1, Pitpnm2 and Drosophila rdgB. These genes share the PITP (phosphatidylinositol tranfer protein) domain which aids transfer of phosphatidylinositol (PtdIns) between different membrane compartments. Although the mammalian and fly orthologs are highly expressed in the nervous systems, their neuronal functions remain to be elucidated.We found M01F1.7 is expressed broadly in the nervous system. The defects in chemotaxis and learning were partially rescued by expression of M01F1.7 cDNA in the ASER neuron. In ASER, a M01F1.7::GFP fusion protein showed a punctate localization mainly in the cell body and the axon, suggesting that M01F1.7 may transport PtIns to the synaptic regions.Importantly,
dgk-1 suppressed the reduced NaCl attraction in M01F1.7
(tm1500), indicating that DAG signaling is decreased in
tm1500. However, the defective learning phenotype of
tm1500 was not suppressed by
dgk-1, implying a role for other PIs in learning. These results suggest a working model in which M01F1.7 transports PtdIns to synapstic region for production of DAG and PIs to dynamically regulate sensory behaviors.