Characterization of ADP-ribosyl cyclase 1-like (ARC1-like) activity and NAADP signaling during slow muscle cell development in zebrafish embryos

Abstract

We recently demonstrated the requirement of two-pore channel type 2 (TPC2)-mediated Ca2+ release during slow muscle cell differentiation and motor circuit maturation in intact zebrafish embryos. However, the upstream trigger of TPC2/Ca2+ signaling during these developmental processes remains unclear. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+ mobilizing messenger, which is suggested to target TPC2 in mediating the release of Ca2+ from acidic vesicles. Here, we report the molecular cloning of the zebrafish ADP ribosyl cyclase (ARC) homolog (i.e., ARC1-like), which is the putative enzyme for generating NAADP. We characterized the expression of the arc1-like transcript and the NAADP level between ~16 hours post-fertilization (hpf) and ~48 hpf in whole zebrafish embryos. We showed that when ARC1-like was fused with either EGFP or tdTomato, it was localized in the plasma membrane, and associated with intracellular organelles, such as the acidic vesicles, Golgi complex and sarcoplasmic reticulum, in primary muscle cell cultures. Morpholino (MO)-mediated knockdown of arc1-like or pharmacological inhibition of ARC1 (via treatment with nicotinamide), led to an attenuation of Ca2+ signaling and disruption of slow muscle cell development. In addition, the injection of arc1-like mRNA into ARC1-like morphants partially rescued the Ca2+ signals and slow muscle cell development. Together, our data might suggest a link between ARC1-like, NAADP, TPC2 and Ca2+ signaling during zebrafish myogenesis.

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

“…TPC2 is an intracellular voltage- and ligand-gated ion channel and a key downstream effector of PI(3,5)P2 signalling in lysosomes (Patel 2015 ). Interestingly, PIKfyve (Martin et al 2013 ) and TPC2 (Kelu et al 2018 ) are expressed in the brain, suggesting a possible role of these molecules in SARS-CoV-2 neuroinfection. Ou et al ( 2020 ) demonstrated that the PIKfyve inhibitor, YM201636 or apilimod, and the TPC2 inhibitor, tetrandrine, effectively inhibited the entry of CoV virion into 293/hACE2 cells (Ou et al 2020 ).…”

Targeting Two-Pore Channels: Current Progress and Future Challenges

“…This finding is consistent with previous studies that identified a role for NAADP/TPC2-induced Ca 2+ signals in neuronal and skeletal muscle differentiation [ 16 , 19 , 20 ]. Moreover, ADP-ribosyl cyclase 1-like (ARC1-like) was linked to NAADP-mediated Ca 2+ release via TPC2 in zebrafish myogenesis [ 21 ]. However, TPC2 involvement in autophagy is debated [ 22.…”

Evolutionary Aspects of TRPMLs and TPCs

“…Furthermore, Andrew Miller's group discovered a putative link between ARC1-like (zebra fish ADP ribosyl cyclase (ARC) homolog) and NAADP generation, TPC2, and Ca 2+ signaling during zebrafish myogenesis. Knock down or pharmacological inhibition of ARC1-like leads to an attenuation of Ca 2+ signaling and disruption of slow muscle cell development [133]. In single-or multi-celled phagotrophic bacterivores, Dictyostelium discoideum TPC2 disruption leads to delayed development and prolonged growth in culture, delaying expression of early developmental genes.…”