@article {164004, title = {EB1 surges promote ciliary outer-segment growth through periodic tubulin influxes into the Drosophila olfactory cilia.}, journal = {J Cell Sci}, volume = {139}, year = {2026}, month = {2026 Jan 15}, abstract = {

Sensory cilia have a complex bipartite architecture containing 9+0 connecting cilia at the inner segment and singlet microtubule-supported highly membranous outer segments essential for receptor display. The mechanisms underlying the formation of such highly branched morphology and its microtubule-rich ciliary cytoskeleton are unclear. Here, we show that individual olfactory cilium inside the large basiconic sensillum grows in episodic steps following several pulsatile influxes of tubulin in developing Drosophila antenna. Transient elevations of the microtubule end-binding protein EB1 precede the tubulin influx events. We also demonstrate that EB1 interacts explicitly with the cargo-binding tail domain of Drosophila KLP68D, a kinesin-2β orthologue. Loss of EB1 in olfactory neurons during the outer segment growth reduces the tubulin influx and affects cilia stability. Finally, we show that the EB1 and tubulin influxes into the distal outer segment of the olfactory cilia require kinesin-2. Altogether, our findings elucidate a role of active EB1 transport in promoting the growth and stability of long-lived metazoan cilia involved in sensory perception.

}, keywords = {Animals, Cilia, Drosophila melanogaster, Drosophila Proteins, Kinesins, Microtubule-Associated Proteins, Microtubules, Olfactory Receptor Neurons, Tubulin}, issn = {1477-9137}, doi = {10.1242/jcs.263625}, url = {https://pubmed.ncbi.nlm.nih.gov/41630694/}, author = {Agarwal, Riddhi Girdhar and Iyer, Saishree Suresh and Barbora, Ayan and Desai, Minita and Gadgil, Yogesh and Jana, Swadhin Chandra and Ray, Krishanu} } @article {155676, title = {Ca2+ binding to Esyt modulates membrane contact site density in Drosophila photoreceptors.}, journal = {J Cell Biol}, volume = {224}, year = {2025}, month = {2025 May 05}, abstract = {

Membrane contact sites (MCS) between the plasma membrane (PM) and endoplasmic reticulum (ER) regulate Ca2+ influx. However, the mechanisms by which cells modulate ER-PM MCS density are not understood, and the role of Ca2+, if any, in regulating these is unknown. We report that in Drosophila photoreceptors, MCS density is regulated by the Ca2+ channels, TRP and TRPL. Regulation of MCS density by Ca2+ is mediated by Drosophila extended synaptotagmin (dEsyt), a protein localized to ER-PM MCS and previously shown to regulate MCS density. We find that the Ca2+-binding activity of dEsyt is required for its function in vivo. dEsytCaBM, a Ca2+ non-binding mutant of dEsyt is unable to modulate MCS structure. Further, reconstitution of dEsyt null photoreceptors with dEsytCaBM is unable to rescue ER-PM MCS density and other key phenotypes. Thus, our data supports a role for Ca2+ binding to dEsyt in regulating ER-PM MCS density in photoreceptors thus tuning signal transduction during light-activated Ca2+ influx.

}, keywords = {Animals, Calcium, Calcium Signaling, Cell Membrane, Drosophila melanogaster, Drosophila Proteins, Endoplasmic Reticulum, Photoreceptor Cells, Invertebrate, Synaptotagmins, Transient Receptor Potential Channels}, doi = {10.1083/jcb.202407190}, author = {Nath, Vaisaly R and Krishnan, Harini and Mishra, Shirish and Raghu, Padinjat} } @article {158507, title = {Conserved biochemical activity and function of phosphatidylinositol 5 phosphate 4 kinase regulates growth \& development}, year = {2025}, abstract = {

Co-ordination of function between multiple cells, mediated by hormones or growth factors, is a critical requirement for multi-cellularity. Phosphoinositides, generated by lipid kinase activity, are second messengers that mediate such signalling. Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) is a lipid kinase that phosphorylates phosphatidylinositol 5-phosphate (PI5P) to generate phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2]. A comprehensive bioinformatics analysis of the tree of life, revealed that PIP4K is a metazoan-specific enzyme, but with homologs in choanoflagellates. We find that PIP4K from the sponge\ Amphimedon queenslandica\ (AqPIP4K), regarded as the earliest evolved metazoan, shows biochemical activity highly conserved with human PIP4K. Further, AqPIP4K was able to rescue the reduced cell size, growth and development of a\ Drosophila\ PIP4K mutant. These phenotypes are regulated through activity of the insulin receptor, a member of the receptor tyrosine kinase family, that is unique to metazoans. Overall, our work defines PIP4K as part of a signal transduction motif required to regulate receptor tyrosine kinase signalling for intercellular communication in the earliest forms of metazoans.

}, keywords = {Amphimedon queenslandica, Drosophila melanogaster, Growth and development, Insulin signalling, Lipid kinase}, doi = {https://doi.org/10.1242/jcs.263881}, url = {https://journals.biologists.com/jcs/article-abstract/doi/10.1242/jcs.263881/368299/Conserved-biochemical-activity-and-function-of?redirectedFrom=PDF}, author = {Krishnan, H and Muzaffar, S and Sharma, S and Ramya, V and Ghosh, A and Sowdhamini, R and Padinjat, R} } @article {152904, title = {Is Drosophila Larval Competition Involved in Incipient Speciation?}, journal = {J Chem Ecol}, volume = {51}, year = {2025}, month = {2025 Jan 22}, pages = {2}, abstract = {

Geographical, ethological, temporal and ecological barriers can affect interbreeding between populations deriving from an ancestral population, this progressively leading to speciation. A rare case of incipient speciation currently occurs between Drosophila melanogaster populations sampled in Zimbabwe (Z) and all other populations (M). This phenomenon was initially characterized by Z females refusing to mate with M males. Despite the fact that Z and M flies produce different amounts of cuticular pheromones, their manipulation and that of other sensory signals exchanged during courtship behavior only marginally rescued the behavioral isolation. To further explore the putative mechanisms involved in this phenomenon, we first assessed the fecundity in matings between Z and M flies. Then, we measured the reproduction and survival in adults resulting of co-cultured Z and M larvae. In these two experiments, Z flies rarely emerged. Z and M larvae produced different amounts of food-derived metabolites which were altered in co-culture condition. This maybe related to the different bacteria composition in the gut and body of Z and M flies. However, the mating behavior of co-cultured flies did not change and their cuticular pheromone profile was slightly altered. Thus, the Z/M larval competition could reinforce the barriers induced by gametic and behavioral isolation processes on this incipient speciation phenomenon.

}, keywords = {Animals, Competitive Behavior, Drosophila melanogaster, Female, Fertility, Genetic Speciation, Larva, Male, Pheromones, Reproduction, Sexual Behavior, Animal}, issn = {1573-1561}, doi = {10.1007/s10886-025-01560-y}, author = {Jean-Fran{\c c}ois, Ferveur and Pratibha, Sanjenbam and Baptiste, Regnier and Jean-Pierre, Farine and J{\'e}r{\^o}me, Cortot and Deepa, Agashe and Claude, Everaerts} } @article {140648, title = {IFT88 maintains sensory function by localising signalling proteins along cilia.}, journal = {Life Sci Alliance}, volume = {7}, year = {2024}, month = {2024 May}, abstract = {

Ciliary defects cause several ciliopathies, some of which have late onset, suggesting cilia are actively maintained. Still, we have a poor understanding of the mechanisms underlying their maintenance. Here, we show r IFT88 (IFT88/nompB) continues to move along fully formed sensory cilia. We further identify Inactive, a TRPV channel subunit involved in hearing and negative-gravitaxis behaviour, and a yet uncharacterised Guanylyl Cyclase 2d (Gucy2d/CG34357) as IFT88 cargoes. We also show IFT88 binding to the cyclase{\textasciiacute}s intracellular part, which is evolutionarily conserved and mutated in several degenerative retinal diseases, is important for the ciliary localisation of Gucy2d. Finally, acute knockdown of both IFT88 and Gucy2d in ciliated neurons of adult flies caused defects in the maintenance of cilium function, impairing hearing and negative-gravitaxis behaviour, but did not significantly affect ciliary ultrastructure. We conclude that the sensory ciliary function underlying hearing in the adult fly requires an active maintenance program which involves IFT88 and at least two of its signalling transmembrane cargoes, Gucy2d and Inactive.

}, keywords = {Animals, Cilia, Drosophila, Drosophila melanogaster, Drosophila Proteins, Hearing}, issn = {2575-1077}, doi = {10.26508/lsa.202302289}, author = {Werner, Sascha and Okenve-Ramos, Pilar and Hehlert, Philip and Zitouni, Sihem and Priya, Pranjali and Mendon{\c c}a, Susana and Sporbert, Anje and Spalthoff, Christian and G{\"o}pfert, Martin C and Jana, Swadhin Chandra and Bettencourt-Dias, M{\'o}nica} } @article {137339, title = {Tracking Sugar-Elicited Local Searching Behavior in Drosophila.}, journal = {J Vis Exp}, year = {2023}, month = {2023 Nov 17}, abstract = {

Foraging behavior is essential for the survival of organisms as it enables them to locate and acquire essential food resources. In Drosophila, hunger triggers a distinct search behavior following the consumption of small quantities of a sugar solution. This report presents a simple experimental setup to study sugar-elicited search behavior with the aim of uncovering the underlying mechanisms. Minute quantities of concentrated sugar solution elicit sustained searching behavior in flies. The involvement of path integration in this behavior has been established, as flies utilize their trajectory to return to the sugar location. The most recent findings provide evidence of temporal modulation in the initiation and intensity of the search behavior after sugar intake. We have also used this setup for artificial activation of specific taste-receptor neurons in the pharynx, which elicits the search behavior. The Drosophila neurogenetic toolkit offers a diverse array of tools and techniques that can be combined with the sugar-elicited search behavior paradigm to study the neural and genetic mechanisms underlying foraging. Understanding the neural basis of hunger-driven searching behavior in flies contributes to the field of neurobiology as a whole, offering insights into the regulatory mechanisms that govern feeding behaviors not only in other organisms but also in humans.

}, keywords = {Animals, Appetitive Behavior, Carbohydrates, Drosophila, Drosophila melanogaster, Drosophila Proteins, Feeding Behavior, Humans, Sugars}, issn = {1940-087X}, doi = {10.3791/65955}, author = {Shakeel, Manal and Kaushik, Shivam and Tanimura, Teiichi and Brockmann, Axel and Kain, Pinky} } @article {854, title = {Ancient dynamin segments capture early stages of host-mitochondrial integration.}, journal = {Proc Natl Acad Sci U S A}, volume = {112}, year = {2015}, month = {2015 Mar 3}, pages = {2800-5}, abstract = {

Eukaryotic cells use dynamins-mechano-chemical GTPases--to drive the division of endosymbiotic organelles. Here we probe early steps of mitochondrial and chloroplast endosymbiosis by tracing the evolution of dynamins. We develop a parsimony-based phylogenetic method for protein sequence reconstruction, with deep time resolution. Using this, we demonstrate that dynamins diversify through the punctuated transformation of sequence segments on the scale of secondary-structural elements. We find examples of segments that have remained essentially unchanged from the 1.8-billion-y-old last eukaryotic common ancestor to the present day. Stitching these together, we reconstruct three ancestral dynamins: The first is nearly identical to the ubiquitous mitochondrial division dynamins of extant eukaryotes, the second is partially preserved in the myxovirus-resistance--like dynamins of metazoans, and the third gives rise to the cytokinetic dynamins of amoebozoans and plants and to chloroplast division dynamins. The reconstructed sequences, combined with evolutionary models and published functional data, suggest that the ancestral mitochondrial division dynamin also mediated vesicle scission. This bifunctional protein duplicated into specialized mitochondrial and vesicle variants at least three independent times--in alveolates, green algae, and the ancestor of fungi and metazoans-accompanied by the loss of the ancient prokaryotic mitochondrial division protein FtsZ. Remarkably, many extant species that retain FtsZ also retain the predicted ancestral bifunctional dynamin. The mitochondrial division apparatus of such organisms, including amoebozoans, red algae, and stramenopiles, seems preserved in a near-primordial form.

}, keywords = {Animals, Arabidopsis, Caenorhabditis elegans, Chloroplasts, Dictyostelium, Drosophila melanogaster, Dynamins, Evolution, Molecular, Humans, Mitochondria, Mitochondrial Dynamics, Saccharomyces cerevisiae, Schizosaccharomyces}, issn = {1091-6490}, doi = {10.1073/pnas.1407163112}, author = {Purkanti, Ramya and Thattai, Mukund} } @article {896, title = {Cytoskeletal control of nuclear morphology and chromatin organization.}, journal = {J Mol Biol}, volume = {427}, year = {2015}, month = {2015 Feb 13}, pages = {695-706}, abstract = {

The nucleus is sculpted toward various morphologies during cellular differentiation and development. Alterations in nuclear shape often result in changes to chromatin organization and genome function. This is thought to be reflective of its role as a cellular mechanotransducer. Recent evidence has highlighted the importance of cytoskeletal organization in defining how nuclear morphology regulates chromatin dynamics. However, the mechanisms underlying cytoskeletal control of chromatin remodeling are not well understood. We demonstrate here the differential influence of perinuclear actin- and microtubule-driven assemblies on nuclear architecture using pharmacological inhibitors and targeted RNA interference knockdown of cytoskeleton components in Drosophila cells. We find evidence that the loss of perinuclear actin assembly results in basolateral enhancement of microtubule organization and this is reflected functionally by enhanced nuclear dynamics. Cytoskeleton reorganization leads to nuclear lamina deformation that influences heterochromatin localization and core histone protein mobility. We also show that modulations in actin-microtubule assembly result in differential gene expression patterns. Taken together, we suggest that perinuclear actin and basolateral microtubule organization exerts mechanical control on nuclear morphology and chromatin dynamics.

}, keywords = {Actins, Animals, Cell Nucleus, Chromatin Assembly and Disassembly, Cytoskeleton, Drosophila melanogaster, Gene Expression Regulation, Histones, Mechanotransduction, Cellular, Nuclear Proteins}, issn = {1089-8638}, doi = {10.1016/j.jmb.2014.09.008}, author = {Ramdas, Nisha M and Shivashankar, G V} } @article {877, title = {A dPIP5K dependent pool of phosphatidylinositol 4,5 bisphosphate (PIP2) is required for G-protein coupled signal transduction in Drosophila photoreceptors.}, journal = {PLoS Genet}, volume = {11}, year = {2015}, month = {2015 Jan}, pages = {e1004948}, abstract = {

Multiple PIP2 dependent molecular processes including receptor activated phospholipase C activity occur at the neuronal plasma membranes, yet levels of this lipid at the plasma membrane are remarkably stable. Although the existence of unique pools of PIP2 supporting these events has been proposed, the mechanism by which they are generated is unclear. In Drosophila photoreceptors, the hydrolysis of PIP2 by G-protein coupled phospholipase C activity is essential for sensory transduction of photons. We identify dPIP5K as an enzyme essential for PIP2 re-synthesis in photoreceptors. Loss of dPIP5K causes profound defects in the electrical response to light and light-induced PIP2 dynamics at the photoreceptor membrane. Overexpression of dPIP5K was able to accelerate the rate of PIP2 synthesis following light induced PIP2 depletion. Other PIP2 dependent processes such as endocytosis and cytoskeletal function were unaffected in photoreceptors lacking dPIP5K function. These results provide evidence for the existence of a unique dPIP5K dependent pool of PIP2 required for normal Drosophila phototransduction. Our results define the existence of multiple pools of PIP2 in photoreceptors generated by distinct lipid kinases and supporting specific molecular processes at neuronal membranes.

}, keywords = {Animals, Cell Membrane, Cytoskeleton, Drosophila, Drosophila melanogaster, Light Signal Transduction, Membrane Proteins, Ocular Physiological Phenomena, Phosphatidylinositol 4,5-Diphosphate, Phosphoinositide Phospholipase C, Phosphotransferases (Alcohol Group Acceptor), Photoreceptor Cells, Retina, Signal Transduction}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1004948}, author = {Chakrabarti, Purbani and Kolay, Sourav and Yadav, Shweta and Kumari, Kamalesh and Nair, Amit and Trivedi, Deepti and Raghu, Padinjat} } @article {885, title = {Phosphoinositide signalling in Drosophila.}, journal = {Biochim Biophys Acta}, volume = {1851}, year = {2015}, month = {2015 Jun}, pages = {770-84}, abstract = {

Phosphoinositides (PtdInsPs) are lipids that mediate a range of conserved cellular processes in eukaryotes. These include the transduction of ligand binding to cell surface receptors, vesicular transport and cytoskeletal function. The nature and functions of PtdInsPs were initially elucidated through biochemical experiments in mammalian cells. However, over the years, genetic and cell biological analysis in a range of model organisms including S. cerevisiae, D. melanogaster and C. elegans have contributed to an understanding of the involvement of PtdInsPs in these cellular events. The fruit fly Drosophila is an excellent genetic model for the analysis of cell and developmental biology as well as physiological processes, particularly analysis of the complex relationship between the cell types of a metazoan in mediating animal physiology. PtdInsP signalling pathways are underpinned by enzymes that synthesise and degrade these molecules and also by proteins that bind to these lipids in cells. In this review we provide an overview of the current understanding of PtdInsP signalling in Drosophila. We provide a comparative genomic analysis of the PtdInsP signalling toolkit between Drosophila and mammalian systems. We also review some areas of cell and developmental biology where analysis in Drosophila might provide insights into the role of this lipid-signalling pathway in metazoan biology. This article is part of a Special Issue entitled Phosphoinositides.

}, keywords = {Animals, CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase, Drosophila melanogaster, Drosophila Proteins, Gene Expression Regulation, Isoenzymes, Phosphatidylinositol 4,5-Diphosphate, Phosphoinositide Phospholipase C, Phospholipid Transfer Proteins, Receptors, Cell Surface, Signal Transduction, Species Specificity, Substrate Specificity}, issn = {0006-3002}, doi = {10.1016/j.bbalip.2014.10.010}, author = {Balakrishnan, Sruthi S and Basu, Urbashi and Raghu, Padinjat} }