Biology subjects

Martin, H. R.

Publications and source records attributed to Martin, H. R..

3 recordsLinked to original sources

bioRxiv2026

HCMV glycoprotein B, but not the pentameric complex, is a key target of antibody-mediated phagocytosis

Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects globally with devastating fetal health outcomes, and there is currently no HCMV vaccine available. Glycoprotein B (gB) and the pentameric complex (PC) are immunodominant HCMV envelope proteins and candidates of interest in vaccine development due to their ability to elicit strong anti-HCMV neutralization responses. Recent evidence implicates non-neutralizing antibody functions in protection from vertical HCMV transmission, but the involvement of gB and PC in these responses remains incompletely understood. We evaluated immune responses against HCMV elicited by a gB protein subunit vaccine with and without PC in a preclinical rabbit study. Despite improved neutralization and inhibition of cell-associated viral spread, the inclusion of PC did not enhance antibody-mediated phagocytosis or Fc{gamma}R activation against HCMV virions or infected cells compared to gB alone. We additionally found a reduction in phagocytosis function by an HCMV hyperimmune globulin when blocked against gB, but not PC, suggesting that gB is a target of phagocytosis-mediating antibodies while PC is not. Given that antibody-mediated phagocytosis but not neutralization has been associated with protection from vertical HCMV transmission, these findings support the continued assessment of gB, but not PC, as a vaccine antigen for the prevention of vertical transmission via non-neutralizing antibodies to reduce the congenital HCMV burden worldwide.

immunology↗

bioRxiv2025

KV1.8 (Kcna10) potassium channels enhance fast, linear signaling in vestibular hair cells and facilitate vestibulomotor reflexes and balance

Vestibular hair cells (HCs) faithfully and rapidly detect head motions and gravity, driving motor reflexes that stabilize balance and gaze during locomotion. With the transition from water to land, the amniote vestibular inner ear added type I HCs, which differ from amniote type II HCs and anamniote HCs by their large calyx afferent synapse, non-quantal afferent transmission, and a large, low-voltage-activated K+ conductance (gK,L). We recently showed that both gK,L and the major type II K+ conductances (A-type and delayed rectifier) require KV1.8 (Kcna10) subunits. Here we compared KV1.8-null (Kcna10-/-) and control animals to see how KV1.8 affects function as measured by receptor potentials and nonquantal postsynaptic potentials evoked by direct hair bundle motions, and by vestibulomotor behaviors. Recordings were taken from extrastriolar zones of the utricle. In both HC types, KV1.8 affected receptor potentials by reducing response time and gain, increasing dampening, and expanding the frequency bandwidth toward high frequencies. Effects are most prominent in type I HCs: lowpass corner frequencies of receptor potentials in Kcna10-/- HCs of both types were [~]20 Hz, vs. [~]400 Hz in control type I and [~]70 Hz in control type II. We recorded nonquantal postsynaptic potentials from extrastriolar calyces, and found that the synaptic transfer function had lower gain and greater phase lag in Kcna10-/- mice. In behavioral tests, Kcna10-/- mice had vestibular-ocular reflexes with different response dynamics at low frequencies, impaired performance on a narrow balance beam, abnormal body posture and abnormal head motions in water and on land, and also rarely assumed bipedal stances. These vestibulomotor deficits in Kcna10-/- mice likely reflect the changes noted in HCs, where KV1.8 expression is concentrated; that is, slower signaling of high-frequency head motions by Kcna10-/- HCs fails to fully stabilize body and head position during locomotion. Thus, gK,L (KV1.8) contributes to fast signal transmission in the amniote vestibular inner ear and supports improved performance on challenging vestibulomotor tasks. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/634388v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@126570borg.highwire.dtl.DTLVardef@1cab5borg.highwire.dtl.DTLVardef@36240corg.highwire.dtl.DTLVardef@789617_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

The potassium channel subunit KV1.8 (Kcna10) is essential for the distinctive outwardly rectifying conductances of type I and II vestibular hair cells

In amniotes, head motions and tilt are detected by two types of vestibular hair cells (HCs) with strikingly different morphology and physiology. Mature type I HCs express a large and very unusual potassium conductance, gK,L, which activates negative to resting potential, confers very negative resting potentials and low input resistances, and enhances an unusual non-quantal transmission from type I cells onto their calyceal afferent terminals. Following clues pointing to KV1.8 (KCNA10) in the Shaker K channel family as a candidate gK,L subunit, we compared whole-cell voltage-dependent currents from utricular hair cells of KV1.8-null mice and littermate controls. We found that KV1.8 is necessary not just for gK,L but also for fast-inactivating and delayed rectifier currents in type II HCs, which activate positive to resting potential. The distinct properties of the three KV1.8-dependent conductances may reflect different mixing with other KV subunits that are reported to be differentially expressed in type I and II HCs. In KV1.8-null HCs of both types, residual outwardly rectifying conductances include KV7 (KCNQ) channels. Current clamp records show that in both HC types, KV1.8-dependent conductances increase the speed and damping of voltage responses. Features that speed up vestibular receptor potentials and non-quantal afferent transmission may have helped stabilize locomotion as tetrapods moved from water to land. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/563853v3_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1409188org.highwire.dtl.DTLVardef@12aaa0org.highwire.dtl.DTLVardef@18000e0org.highwire.dtl.DTLVardef@b995c5_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗