Regulation of neuronal survival and morphology by the E3 ubiquitin ligase RNF157.

Neuronal health is essential for the long-term integrity of the brain. In this study, we characterized the novel E3 ubiquitin ligase ring finger protein 157 (RNF157), which displays a brain-dominant expression in mouse. RNF157 is a homolog of the E3 ligase mahogunin ring finger-1, which has been previously implicated in spongiform neurodegeneration. We identified RNF157 as a regulator of survival in cultured neurons and established that the ligase activity of RNF157 is crucial for this process. We also uncovered that independently of its ligase activity, RNF157 regulates dendrite growth and maintenance. We further identified the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65) as an interactor and proteolytic substrate of RNF157 in the control of neuronal survival. Here, the nuclear localization of Fe65 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. In summary, we described that the E3 ligase RNF157 regulates important aspects of neuronal development.

A doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia.

Mechanoreceptors are sensory cells that transduce mechanical stimuli into electrical signals and mediate the perception of sound, touch and acceleration. Ciliated mechanoreceptors possess an elaborate microtubule cytoskeleton that facilitates the coupling of external forces to the transduction apparatus. In a screen for genes preferentially expressed in Drosophila campaniform mechanoreceptors, we identified DCX-EMAP, a unique member of the EMAP family (echinoderm-microtubule-associated proteins) that contains two doublecortin domains. DCX-EMAP localizes to the tubular body in campaniform receptors and to the ciliary dilation in chordotonal mechanoreceptors in Johnston's organ, the fly's auditory organ. Adult flies carrying a piggyBac insertion in the DCX-EMAP gene are uncoordinated and deaf and display loss of mechanosensory transduction and amplification. Electron microscopy of mutant sensilla reveals loss of electron-dense materials within the microtubule cytoskeleton in the tubular body and ciliary dilation. Our results establish a catalogue of candidate genes for Drosophila mechanosensation and show that one candidate, DCX-EMAP, is likely to be required for mechanosensory transduction and amplification.

A generalization of the van-der-Pol oscillator underlies active signal amplification in Drosophila hearing.

The antennal hearing organs of the fruit fly Drosophila melanogaster boost their sensitivity by an active mechanical process that, analogous to the cochlear amplifier of vertebrates, resides in the motility of mechanosensory cells. This process nonlinearly improves the sensitivity of hearing and occasionally gives rise to self-sustained oscillations in the absence of sound. Time series analysis of self-sustained oscillations now unveils that the underlying dynamical system is well described by a generalization of the van-der-Pol oscillator. From the dynamic equations, the underlying amplification dynamics can explicitly be derived. According to the model, oscillations emerge from a combination of negative damping, which reflects active amplification, and a nonlinear restoring force that dictates the amplitude of the oscillations. Hence, active amplification in fly hearing seems to rely on the negative damping mechanism initially proposed for the cochlear amplifier of vertebrates.

Power gain exhibited by motile mechanosensory neurons in Drosophila ears.

In insects and vertebrates alike, hearing is assisted by the motility of mechanosensory cells. Much like pushing a swing augments its swing, this cellular motility is thought to actively augment vibrations inside the ear, thus amplifying the ear's mechanical input. Power gain is the hallmark of such active amplification, yet whether and how much energy motile mechanosensory cells contribute within intact auditory systems has remained uncertain. Here, we assess the mechanical energy provided by motile mechanosensory neurons in the antennal hearing organs of Drosophila melanogaster by analyzing the fluctuations of the sound receiver to which these neurons connect. By using dead WT flies and live mutants (tilB(2), btv(5P1), and nompA(2)) with defective neurons as a background, we show that the intact, motile neurons do exhibit power gain. In WT flies, the neurons lift the receiver's mean total energy by 19 zJ, which corresponds to 4.6 times the energy of the receiver's Brownian motion. Larger energy contributions (200 zJ) associate with self-sustained oscillations, suggesting that the neurons adjust their energy expenditure to optimize the receiver's sensitivity to sound. We conclude that motile mechanosensory cells provide active amplification; in Drosophila, mechanical energy contributed by these cells boosts the vibrations that enter the ear.

Motion generation by Drosophila mechanosensory neurons.

In Drosophila melanogaster, hearing is supported by mechanosensory neurons transducing sound-induced vibrations of the antenna. It is shown here that these neurons additionally generate motions that mechanically drive the antenna and tune it to relevant sounds. Motion generation in the Drosophila auditory system is betrayed by the auditory mechanics; the antenna of the fly nonlinearly alters its tuning as stimulus intensity declines and oscillates spontaneously in the absence of sound. The susceptibility of auditory motion generation to mechanosensory mutations shows that motion is generated by mechanosensory neurons. Motion generation depends on molecular components of the mechanosensory transduction machinery (NompA, NompC, Btv, and TilB), apparently involving mechanical activity of ciliated dendrites and microtubule-dependent motors. Hence, in analogy to vertebrate hair cells, the mechanosensory neurons of the fly serve dual, transducing, and actuating roles, documenting a striking functional parallel between the vertebrate cochlea and the ears of Drosophila.

atonal is required for exoskeletal joint formation in the Drosophila auditory system.

Hearing relies on the delicate arrangement of mechanoreceptor neurones and an acoustomechanical interface. The concerted action of these neural and non-neural components is essential to audition, raising the question of whether they also develop in a concerted way. Drosophila hears with its antennae. A specialized antennal joint allows the distal part of the antenna to vibrate in response to sound and, thus, to serve as the sound receiver. This receiver's vibration is transduced by a chordotonal sense organ (CHO) that is closely associated with the joint. Here, we report that atonal (ato), the proneural gene for CHOs, is required for the formation of this antennal joint. Biophysical measurements in hemi- and homozygous ato(1) mutant flies show that, in addition to eliminating the auditory CHO, loss of ato function makes the antennal receiver insensitive to sound, impairing its auditory function. Anatomically, the cause for this mechanical effect resides in the deprivation of mobile exoskeletal joint structures. Hence, ato, the homologue of mouse Math1, is required for the formation of both the auditory CHO and joint, providing a genetic link between the very neural and exoskeletal components that together transform fly antennae into ears.

Acoustic sensitivity of fly antennae.

The vast majority of higher flies - the brachycerans - is endowed with strikingly similar antennal morphologies and elaborate antennal mechanosensory organs. Thus far, however, the function of audition has been attributed only to the antennae of Drosophilid and Tephritid flies. Antennal mechanical sensitivity to sound is now documented in a broad range of fly species. These results highlight the wide occurrence of audition in as many as 120,000 species of higher Diptera. Antenna-based audition, as defined by the capacity of sensing the mechanical vibrations of the antenna in response to sound, thus appears to constitute an ubiquitous sensory capacity among higher flies. Functionally, antennal hearing can be used in the contexts of intraspecific acoustic signalling, flight control, and putatively close-range echolocation.

Active auditory mechanics in mosquitoes.

In humans and other vertebrates, hearing is improved by active contractile properties of hair cells. Comparable active auditory mechanics is now demonstrated in insects. In mosquitoes, Johnston's organ transduces sound-induced vibrations of the antennal flagellum. A non-muscular 'motor' activity enhances the sensitivity and tuning of the flagellar mechanical response in physiologically intact animals. This motor is capable of driving the flagellum autonomously, amplifying sound-induced vibrations at specific frequencies and intensities. Motor-related electrical activity of Johnston's organ strongly suggests that mosquito hearing is improved by mechanoreceptor motility.

Karyotype comparison and phylogenetic relationships of Pipistrellus-like bats (Vespertilionidae; Chiroptera; Mammalia).

Detailed karyotype descriptions of 20 Pipistrellus-like bat species belonging to the family Vespertilionidae are presented. For the first time, chromosomal complements of four species, i.e. Pipistrellus stenopterus (2n = 32), P. javanicus (2n = 34), Hypsugo eisentrauti (2n = 42) and H. crassulus (2n = 30) are reported. A Pipistrellus kuhlii-like species from Madagascar represents a separate species distinguished from the European Pipistrellus kuhlii (2n = 44) by a diploid chromosome number of 42. Banded karyotypes are presented for the first time for Scotozous dormeri, Hypsugo capensis, Hesperoptenus blanfordi, Tylonycteris pachypus and robustula. Chromosomal evolution in the family Vespertilionidae is characterized by the conservation of entire chromosomal arms and reductions in diploid chromosome number via Robertsonian fusions. Less frequently, centric fissions, para- and pericentric inversions and centromere shifts were found to have occurred. In several cases a certain type of chromosomal change predominates in a karyotype. Examples of this are the acquisition of interstitial heterochromatic bands in Tylonycteris robustula, and centric shifts in P. javanicus, H. eisentrauti and Hesp. blanfordi. The species examined here belong to three tribes, i.e. Pipistrellini, Vespertilionini and Eptesicini, which are distinguished by chromosomal characteristics. According to our results, the species Pipistrellus (Neoromicia) capensis belongs to the Vespertilionini and not to the Pipistrellini. We therefore propose to elevate the subgenus Neoromicia to generic rank.

Nanometre-range acoustic sensitivity in male and female mosquitoes.

Johnston's sensory organ at the base of the antenna serves as a movement sound detector in male mosquitoes, sensing antennal vibrations induced by the flight sounds of conspecific females. Simultaneous examination of acoustically elicited antennal vibrations and neural responses in the mosquito species Toxorhynchites brevipalpis has now demonstrated the exquisite acoustic and mechanical sensitivity of Johnston's organ in males and, surprisingly, also in females. The female Johnston's organ is less sensitive than that of males. Yet it responds to antennal deflections of +/- 0.0005 degrees induced by +/- 11 nm air particle displacements in the sound field, thereby surpassing the other insect movement sound detectors in sensitivity. These findings strongly suggest that the reception of sounds plays a crucial role in the sensory ecology of both mosquito sexes.

Mosquito hearing: sound-induced antennal vibrations in male and female Aedes aegypti.

Male mosquitoes are attracted by the flight sounds of conspecific females. In males only, the antennal flagellum bears a large number of long hairs and is therefore said to be plumose. As early as 1855, it was proposed that this remarkable antennal anatomy served as a sound-receiving structure. In the present study, the sound-induced vibrations of the antennal flagellum in male and female Aedes aegypti were compared, and the functional significance of the flagellar hairs for audition was examined. In both males and females, the antennae are resonantly tuned mechanical systems that move as simple forced damped harmonic oscillators when acoustically stimulated. The best frequency of the female antenna is around 230 Hz; that of the male is around 380 Hz, which corresponds approximately to the fundamental frequency of female flight sounds. The antennal hairs of males are resonantly tuned to frequencies between approximately 2600 and 3100 Hz and are therefore stiffly coupled to, and move together with, the flagellar shaft when stimulated at biologically relevant frequencies around 380 Hz. Because of this stiff coupling, forces acting on the hairs can be transmitted to the shaft and thus to the auditory sensory organ at the base of the flagellum, a process that is proposed to improve acoustic sensitivity. Indeed, the mechanical sensitivity of the male antenna not only exceeds the sensitivity of the female antenna but also those of all other arthropod movement receivers studied so far.