The Molecular Architecture of Ribbon Presynaptic Terminals

Abstract

The primary receptor neurons of the auditory, vestibular, and visual systems encode a broad range of sensory information by modulating the tonic release of the neurotransmitter glutamate in response to graded changes in membrane potential. The output synapses of these neurons are marked by structures called synaptic ribbons, which tether a pool of releasable synaptic vesicles at the active zone, where glutamate release occurs in response to calcium influx through L-type channels. Ribbons are composed primarily of the protein, RIBEYE, which is unique to ribbon synapses, but cytomatrix proteins that regulate the vesicle cycle in conventional terminals, such as Piccolo and Bassoon, also are found at ribbons. Conventional and ribbon terminals differ, however, in the size, molecular composition, and mobilization of their synaptic vesicle pools. Calcium-binding proteins and plasmamembrane calcium pumps, together with endomembrane pumps and channels, play important roles in calcium handling at ribbon synapses. Taken together, emerging evidence suggests that several molecular and cellular specializations work in concert to support the sustained exocytosis of glutamate that is a hallmark of ribbon synapses. Consistent with its functional importance, abnormalities in a variety of functional aspects of the ribbon presynaptic terminal underlie several forms of auditory neuropathy and retinopathy.

Two pools of vesicles associated with the presynaptic cytosolic projection in Drosophila neuromuscular junctions

“…In addition, many synapses that are able to sustain high rates of neurotransmitter release possess presynaptic cytosolic projections (PCPs), extending from the cytoplasmic matrix, which are believed to facilitate vesicle movements. In mammalian synapses such projections, synaptic ribbons, have been described to be at the presynaptic active zones of sensory neurons in the visual, auditory, and vestibular systems (LoGiudice and Matthews, 2009;Schmitz, 2009;Zanazzi and Matthews, 2009). Homologous structures are also found in invertebrates.…”

Can the ‘neuron theory’ be complemented by a universal mechanism for generic neuronal differentiation

“…They are also expressed in cell types other than neurons such as endocrine (for reviews, see Pang and Südhof 2010;Lang and Jahn 2008) and sensory receptor cells (for reviews, see Zanazzi and Matthews 2009;Ramakrishnan et al 2012). In addition to neuronal, sensory receptor, and endocrine cells, the in cell lineage-terms distant, mast cells also employ the SNARE complex for mediator release (Lorentz et al 2012).…”

“…These include synaptotagmin I, Vamp-2, Snap-25 or Rab3a. These proteins are also found in hair cell ribbon synapses in the inner ear where synaptotagmin I is developmentally downregulated in mice (for reviews, see Zanazzi and Matthews 2009;Ramakrishnan et al 2012). Different from neurons, complexin 1 and 2 are not detected in photoreceptors and hair cells while the protein ribeye appears unique to ribbon synapses.…”

Changes in the Numbers of Ribbon Synapses and Expression of RIBEYE in Salicylate-Induced Tinnitus

“…Ribbon synapses, the synaptic terminals of IHCs, function as synaptic connections between IHCs and afferent nerve endings of the spiral ganglion neurons by releasing proteinaceous neurotransmitters from synaptic vesicles near the active zones of IHCs [22,23,24,25]. The normalization of IHC synaptic ribbons is essential for hearing [26].…”

“…IHCs are responsible for transmitting signals of sound frequency and intensity to the central nervous system (CNS) in mammals [21]. The synaptic terminals of IHCs are ribbon synapses, a type of special proteinaceous organelle that tethers large numbers of synaptic vesicles near the active zone where neurotransmission occurs [22]. Ribbon synapses acquired their name due to their ribbon-shaped spatial distribution, and they function as a synaptic connection between IHCs and the afferent nerve endings of spiral ganglion neurons by releasing neurotransmitters [23,24,25].…”