Watching Calcium Channel Subunit Trafficking in C. elegans
Kelly H. Oh, Ame Xiong, Jun-yong Choe, Janet E. Richmond, and Hongkyun Kim
(see pages 5142–5157)
Voltage-sensing calcium ion channels, and the CaV2 channel in particular, play an integral role in regulating synaptic neurotransmission at presynaptic active zones (AZs). CaV2 consists of a pore-forming α subunit, also known as UNC-2, as well as two auxiliary subunits, a β (CCB-1) and an α2δ subunit (UNC-36). The two smaller subunits, one intracellular and one extracellular, were known to play a part in the channel's function, but whether they also aid in channel trafficking to the synapse remained unknown. Protein assembly is a complex and regulated process; membrane-resident proteins typically stay in the endoplasmic reticulum (ER) until accessory subunits are available, and may undergo selective degradation when they are not. Evidence is mixed as to what happens between CaV2 subunits upon exit from ER and trafficking to the plasma membrane, a question that has been complicated because the subunits are encoded by four genes with multiple variants. Now Oh et al. take advantage of the genetic simplicity of Caenorhabditis elegans in which only one gene encodes each subunit. The researchers used CRISPR to endogenously fluorescently label subunit proteins to visualize the localization of CaV2 channel subunits in vivo and made various mutations. The results showed that UNC-2 trafficking to the presynaptic terminal did not require the CCB-1 and UNC-36 subunits, but that those proteins were needed for stable synaptic localization and structural integrity. Conversely, and somewhat surprisingly, UNC-2 was required for CCB-1 and UNC-36 to stay at the AZ; without it the subunits diffused to axonal regions.
Structural model of UNC-2, CCB-1, and fluorescently tagged UNC-36.
Tonotopy in the Mammalian Cochlear Apex
Alberto Recio-Spinoso, Wei Dong, and John S. Oghalai
(see pages 5172–5179)
Across sensory modalities, a key organizing principle is the mapping of specific sensory inputs in a spatially ordered manner at multiple levels, from primary afferents to higher cortex. In the case of the auditory system, that mapping is called tonotopy, in which neurons tuned to specific frequencies map across structures, extending even to the cochlea, the primary sensory organ for hearing. Cochlear tonotopy was first described by Georg V. Békésy in experiments on human cadavers in the middle of the last century and has more recently been shown in rodents. But although the tonotopy pattern is well mapped out at the base of the cochlea, where high-frequency stimuli evoke the biggest responses, there is little evidence for what researchers have long assumed would be low-frequency tuning at the cochlear apex. In this week's issue of the Journal of Neuroscience, Recio-Spinoso et al. use optical coherence tomography to record sound-evoked cochlear responses at the apex of live gerbils, guinea pigs, and chinchillas. Responses recorded at sites 400 μm apart from one another on the cochlear apex showed evidence for tonotopy, with both locations responding similarly to 200 Hz signals, but with smaller responses to 600 Hz signals at the more apical site, demonstrating tuning to lower frequency signals at the apex. More apical responses also had a different shape than basal sites. The response frequency also shifted at higher stimulus levels. Another product of Békésy's early work was his proposed traveling wave theory, which states that a wave takes more time to travel to the cochlear apex. The current findings were consistent with the traveling wave theory. Although tonotopy had been demonstrated previously in mice, the current work extends the findings to three mammals with low-frequency hearing similar to that of humans.
Footnotes
This Week in The Journal was written by Stephani Sutherland
