Biology subjects

Taghert, P. H.

Publications and source records attributed to Taghert, P. H..

4 recordsLinked to original sources

bioRxiv2022

The incidence of candidate binding sites for β-arrestin in Drosophila neuropeptide GPCRs

To support studies of neuropeptide neuromodulation, I have studied beta-arrestin binding sites (BBSs) by evaluating the incidence of BBS sequences among the C terminal tails (CTs) of each of the 49 Drosophila melanogaster neuropeptide GPCRs. BBS were identified by matches with a prediction derived from structural analysis of rhodopsin:arrestin and vasopressin receptor: arrestin complexes (1). To increase the rigor of the identification, I determined the conservation of BBS sequences between two long-diverged species D. melanogaster and D. virilis. There is a great diversity in the profile of BBSs in this group of GPCRs. I present evidence for conserved BBSs in a majority of the Drosophila neuropeptide GPCRs; notably some have no conserved BBS sequences. In addition, certain GPCRs display numerous conserved compound BBSs, and many GPCRs display BBS-like sequences in their intracellular loop (ICL) domains as well. Finally, 20 of the neuropeptide GPCRs are expressed as protein isoforms that vary in their CT domains. BBS profiles are typically different across related isoforms suggesting a need to diversify and regulate the extent and nature of GPCR:arrestin interactions. This work provides the initial basis to initiate future in vivo, genetic analyses in Drosophila to evaluate the roles of arrestins in neuropeptide GPCR desensitization, trafficking and signaling.

physiology↗

bioRxiv2021

Circadian pacemaker neurons display co-phasic rhythms in basal calcium level and in fast calcium fluctuations

Circadian pacemaker neurons in the Drosophila brain display daily rhythms in the levels of intracellular calcium. These calcium rhythms are driven by molecular clocks and are required for normal circadian behavior. To study their biological basis, we employed genetic manipulations in conjunction with in vivo light-sheet microscopy to measure calcium dynamics in individual pacemaker neurons over complete 24-hour periods. We found co-phasic daily rhythms in basal calcium levels and in high frequency calcium fluctuations. Further we found that the rhythms of basal calcium levels require the activity of the IP3R, a channel that mediates calcium fluxes from internal endoplasmic reticulum (ER) calcium stores. Independently, the rhythms of fast calcium fluctuations required the T-type voltage-gated calcium channel, a conductance that mediates extracellular calcium influx. These results suggest that Drosophila molecular clocks regulate IP3R and T-type channels to generate coupled rhythms in basal calcium and in fast calcium fluctuations, respectively. We propose that both internal and external calcium fluxes are essential for circadian pacemaker neurons to provide rhythmic outputs, and thereby regulate the activities of downstream brain centers.

neuroscience↗

bioRxiv2020

Post-mitotic myotubes repurpose the cytokinesis machinery to effect cellular guidance

Embryogenesis depends on a tightly regulated balance between mitosis, differentiation, and morphogenesis. Understanding how the embryo uses a relatively small number of proteins to transition between growth and morphogenesis is a central question of developmental biology, but the mechanisms controlling mitosis and differentiation are considered to be fundamentally distinct. Here we show the mitotic kinase Polo, which regulates all steps of mitosis [1-3], also directs cellular morphogenesis after cell cycle exit. In mitotic cells, the Aurora kinases activate Polo to control a cytoskeletal regulatory module that directs cytokinesis [4-6]. We show that in the post-mitotic mesoderm, the control of Polo activity transitions from the Aurora kinases to the uncharacterized kinase Back Seat Driver (Bsd), where Bsd and Polo cooperate to regulate muscle morphogenesis. Polo and its effectors therefore direct mitosis and cellular morphogenesis, but the transition from growth to morphogenesis is determined by the spatiotemporal expression of upstream activating kinases.

cell biology↗

bioRxiv2018

Morning and Evening Circadian Pacemakers Independently Drive Premotor Centers via a Specific Dopamine Relay

Many animals exhibit morning and evening peaks of locomotor behavior. In Drosophila, previous studies identified two corresponding circadian neural oscillators: M (morning) cells which exhixbit a morning neural activity peak, and E (evening) cells which exhibit a corresponding evening peak of activity. Yet we know little of how these distinct circadian oscillators produce specific outputs that regulate pre-motor circuits to precisely control behavioral episodes. Here we show that the Ring Neurons of the Ellipsoid Body (EB-RNs), a defined pre-motor center, display a spontaneous in vivo neural activity rhythm, with peaks in the morning and in the evening. The two EB-RN activity peaks coincide with the major bouts of locomotor activity and result from independent activation by M and E cells, respectively. Further, M and E cells regulate EB-RNs via two identified dopaminergic neurons PPM3-EB, which project to the EB and which are normally co-active with EB-RNs. Blocking the dopaminergic modulation onto EB-RNs prevents the daily two-peak pattern of neural activity in the EB-RN and greatly impairs circadian locomotor activity. These in vivo findings establish the fundamental elements of a circadian neuronal output pathway: distinct circadian oscillators independently drive a common pre-motor center through the agency of specific dopaminergic interneurons.

neuroscience↗