Neuron‐specific expression of atp6v0c2 in zebrafish CNS

Abstract

*Vacuolar ATPase (V-ATPase) is a multi-subunit enzyme that plays an important role in the acidification of a variety of intracellular compartments. ATP6V0C is subunit c of the V 0 domain that forms the proteolipid pore of the enzyme. In the present study, we investigated the neuron-specific expression of atp6v0c2, a novel isoform of the V-ATPase c-subunit, during the development of the zebrafish CNS. Zebrafish atp6v0c2 was isolated from a genome-wide analysis of the zebrafish mib ta52b mutant designed to identify genes differentially regulated by Notch signaling. Whole-mount in situ hybridization revealed that atp6v0c2 is expressed in a subset of CNS neurons beginning several hours after the emergence of post-mitotic neurons. The ATP6V0C2 protein is co-localized with the presynaptic vesicle marker, SV2, suggesting that it is involved in neurotransmitter storage and/or secretion in neurons. In addition, the loss-of-function experiment suggests that ATP6V0C2 is involved in the control of neuronal excitability. Developmental Dynamics 239:2501-2508,

The zebrafish mutants for the V-ATPase subunits d, ac45, E, H and c and their variable pigment dilution phenotype

“…have the same number of V0-c V-ATPase subunits as in zebrafish (not shown). It was reported that the duplicated gene V0-cb is preferentially expressed in the zebrafish brain, being more specific at the presynaptic vesicles and is regulated by Notch signaling [27]. According to our RT-PCR data V0-ca has a ubiquitous expression (Figure 3B).…”

“…V-ATPases are also important during development in invertebrates [19,20] and vertebrates [21]. Its function is required for specific processes like acquiring left-right asymmetry [22,23], biliary function [24], bone formation [25,26] and neural system development [27,28]. The vacuolar ATPase complex from vertebrates is composed of at least 15 subunits arranged in two functional domains: V1 with subunits A, B, C, D, E, F, G and H and V0 with subunits a, c, c”/b and e. Both domains have a combined molecular weight around 750 kDa.…”

“…Three more insertional mutants for V-ATPase subunits were recently obtained, which are: atp6v1ba la013065Tg (V1-B), atp6v1d la013933Tg (V1-D) and atp6v0a1a la015092Tg (V0-a1a) [31]. Furthermore, knockdown morpholino experiments have also been carried out for V-ATPase subunits genes atp6v0a1a [28], atp6v0b [32], atp6v0ca [33], atp6v0cb [27] and atp6v1a [34]. This means that for 12 out of the 15 V-ATPase subunits there is a mutation or knock down experiment (the exceptions are V1-C, V1-G and V0-e subunits).…”

A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay

“…It is present in endosomes, lysosomes, clathrin-coated vesicles and the Golgi complex, where it is essential to acidification and maintenance of endocytic and exocytic pathways [17]. Experiments in zebrafish embryos suggest a neuron-specific expression of the zebrafish ortholog atp6v0c2 where it is associated with presynaptic vesicles and involved in neurotransmitter storage [18]. PDPK1 (also known as PDK1) is a highly conserved protein kinase that is involved in many different signalling pathways (reviewed in [19]).…”

ATP6V0C Is Associated With Febrile Seizures and Epilepsy With Febrile Seizures Plus

“…As a component of V0 domain of V-ATPase, ATP6V0C forms the proteolipid c-ring of the V-ATPase and plays a pivotal role in synaptic vesicle proton gradient generation and regulation of intra and extracellular pH value (Higashida et al, 2017;Xu et al, 2019). Experiments in zebrafish ortholog revealed that ATP6V0C2 is associated with neurotransmitter storage/secretion and involved in the control of neuronal excitability (Chung et al, 2010). Homozygous ATP6V0C knockout mice exhibit neonatal lethality, abnormal embryonic tissue morphology, and failure of zygotic cell division.…”