RESUMO
The Golgi is the cellular hub for complex glycosylation, controlling accurate processing of complex proteoglycans, receptors, ligands and glycolipids. Its structure and organisation are dependent on golgins, which tether cisternal membranes and incoming transport vesicles. Here, we show that knockout of the largest golgin, giantin, leads to substantial changes in gene expression but only limited effects on Golgi structure. Notably, 22 Golgi-resident glycosyltransferases, but not glycan-processing enzymes or the ER glycosylation machinery, are differentially expressed following giantin ablation. This includes near-complete loss of function of GALNT3 in both mammalian cell and zebrafish models. Giantin-knockout zebrafish exhibit hyperostosis and ectopic calcium deposits, recapitulating phenotypes of hyperphosphatemic familial tumoral calcinosis, a disease caused by mutations in GALNT3. These data reveal a new feature of Golgi homeostasis: the ability to regulate glycosyltransferase expression to generate a functional proteoglycome.
Assuntos
Glicosiltransferases/genética , Complexo de Golgi/genética , Proteínas de Membrana/genética , N-Acetilgalactosaminiltransferases/genética , Animais , Linhagem Celular , Regulação Enzimológica da Expressão Gênica , Complexo de Golgi/enzimologia , Proteínas da Matriz do Complexo de Golgi , Humanos , Mutação , Peixe-Zebra , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
The ear of the bush-cricket, Copiphora gorgonensis, consists of a system of paired eardrums (tympana) on each foreleg. In these insects, the ear is backed by an air-filled tube, the acoustic trachea (AT), which transfers sound from the prothoracic acoustic spiracle to the internal side of the eardrums. Both surfaces of the eardrums of this auditory system are exposed to sound, making it a directionally sensitive pressure difference receiver. A key feature of the AT is its capacity to reduce the velocity of sound propagation and alter the acoustic driving forces at the tympanum. The mechanism responsible for reduction in sound velocity in the AT remains elusive, yet it is deemed to depend on adiabatic or isothermal conditions. To investigate the biophysics of such multiple input ears, we used micro-scanning laser Doppler vibrometry and micro-computed X-ray tomography. We measured the velocity of sound propagation in the AT, the transmission gains across auditory frequencies and the time-resolved mechanical dynamics of the tympanal membranes in C. gorgonensis Tracheal sound transmission generates a gain of approximately 15 dB SPL, and a propagation velocity of ca 255 m s-1, an approximately 25% reduction from free field propagation. Modelling tracheal acoustic behaviour that accounts for thermal and viscous effects, we conclude that reduction in sound velocity within the AT can be explained, among others, by heat exchange between the sound wave and the tracheal walls.
RESUMO
In mammals, hearing is dependent on three canonical processing stages: (i) an eardrum collecting sound, (ii) a middle ear impedance converter, and (iii) a cochlear frequency analyzer. Here, we show that some insects, such as rainforest katydids, possess equivalent biophysical mechanisms for auditory processing. Although katydid ears are among the smallest in all organisms, these ears perform the crucial stage of air-to-liquid impedance conversion and signal amplification, with the use of a distinct tympanal lever system. Further along the chain of hearing, spectral sound analysis is achieved through dispersive wave propagation across a fluid substrate, as in the mammalian cochlea. Thus, two phylogenetically remote organisms, katydids and mammals, have evolved a series of convergent solutions to common biophysical problems, despite their reliance on very different morphological substrates.