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bioRxiv · 10.1101/2020.11.20.392142

Caenorhabditis elegans junctophilin has tissue-specific functions and regulates neurotransmission with extended-synaptotagmin

Piggott, C. A.·Wu, Z.·Nurrish, S.·Xu, S.·Kaplan, J. M.·Chisholm, A. D.·Jin, Y.
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Abstract

The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understanding in vivo functions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the sole C. elegans junctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions. jph-1 null mutants display slow growth and development due to weaker contraction of pharyngeal muscles, leading to reduced feeding. In the body wall muscle, JPH-1 co-localizes with the PM-localized EGL-19 voltage-gated calcium channel and ER-localized UNC-68/RyR calcium channel, and is required for animal movement. We also find an unexpected cell non-autonomous effect of jph-1 in axon regrowth after injury. In neurons, JPH-1 co-localizes with the membrane contact site protein Extended-SYnaptoTagmin 2 (ESYT-2) and modulates neurotransmission. Interestingly, jph-1 and esyt-2 null mutants display mutual suppression in their response to aldicarb, suggesting that JPH-1 and ESYT-1 have antagonistic roles in neuromuscular synaptic transmission. Our genetic double mutant analysis also reveals that jph-1 functions in overlapping pathways with two PM-localized voltage-gated calcium channels, egl-19 and unc-2, and unc-68/RyR for animal health and development. Finally, we show that unc-68/RyR is required for JPH-1 localization to ER-PM puncta. Our data demonstrate important roles for junctophilin in cellular physiology, and also provide insights into how junctophilin functions together with other calcium channels in vivo.

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Piggott, C. A., Wu, Z., Nurrish, S., Xu, S., Kaplan, J. M., Chisholm, A. D., Jin, Y.. 2020-11-21. Caenorhabditis elegans junctophilin has tissue-specific functions and regulates neurotransmission with extended-synaptotagmin. https://doi.org/10.1101/2020.11.20.392142

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