S-026 | Behavioral and physiological role of endogenous Htt in sLNvs of Drosophila melanogaster

Chronobiology
Author: Agustina Bruno-Vignolo | Email: agustinabrunovignolo@gmail.com

Agustina Bruno-Vignolo^1°, Lautaro Duarte^2°, Ana Ricciuti^1°,  Ivana Ducrey^1°, Florencia Fernández-Chiappe^1°, Pedro Ballestero^1°, Marina Propato-Lots^1°,  Cayetana Arnaiz^1°, Tomás Falzone^1°3°, Esteban Beckwith^2°

^1° Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA, CONICET – Partner of the Max Planck Society)
^2° Departamento de Fisiología, Biología Molecular y Celular, FCEN, UBA; Instituto de Fisiología, Biología Molecular y Neurociencias, UBA-CONICET
^3° Instituto de Biología Celular y Neurociencias, Facultad de Medicina, (IBCN-UBA-CONICET)

One of the hallmarks of polyglutamine (polyQ) diseases is the selective vulnerability of different neurons in spite of ubiquitous expression of the pathogenic protein. The reasons behind this specificity underlying neurodegeneration is still an unsolved mystery. In Drosophila melanogaster, it has been shown that the two circadian clusters of lateral ventral neurons (LNvs) exhibit differential responses to the polyQ-expanded huntingtin (Htt) protein. Specifically, while the elongated polyQ tract in Htt selectively impairs the functionality of the small lateral ventral neurons (sLNvs), the large lateral ventral neurons (lLNvs) appear unaffected. However, there is evidence that the disease is not only the result of a gain of function of HttpolyQ, but there is also a concomitant loss of function of wild-type Htt. Htt is ubiquitously expressed in the nervous system and performs various functions, such as serving as a scaffolding protein for molecular motors that mediate the transport of electron-dense vesicles carrying neuromodulators. Drosophila has a homolog of Htt, dHtt, which is conserved in its functional domains but still under-studied. The main objective of this project is to study the function of dHtt in physiology and behavior in order to understand the normal role of this protein. Our data indicate that the downregulation of the fly endogenous huntingtin with dHttRNAi expression in sLNvs impairs circadian rhythmicity and affects sleep behavior.