Abstract

Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that UNC-44/ankyrin acts upstream of UNC-33/CRMP in regulation of a potential kinesin VAB-8 to control gap junction dynamics, and loss-of-function in the UNC-44/UNC-33/VAB-8 pathway suppresses the turnover of gap junction channels. Therefore, we first show a signal pathway including ankyrin, CRMP, and kinesin in regulating gap junctions.

Highlights

  • Gap junctions were first discovered in the myocardium and nerves for their properties of electrical transmission between two adjacent cells [1,2], and they are clusters of channels connecting two cells to allow direct transfer of ions and small molecules [3,4,5]

  • We focus on two of them, unc-44/ankyrin and unc-33/Collapsin response mediator proteins (CRMP)

  • Through genetic analysis in combination with live imaging, we find that UNC-44/ankyrin and UNC-33/CRMP play important roles in gap junction turnover and demonstrate that UNC-44/ankyrin acts upstream of UNC-33/CRMP and VAB-8/ kinesin to regulate the removal of gap junction channels from gap junctions

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Summary

Introduction

Gap junctions were first discovered in the myocardium and nerves for their properties of electrical transmission between two adjacent cells [1,2], and they are clusters of channels connecting two cells to allow direct transfer of ions and small molecules [3,4,5]. Gap junctions play essential roles in many biological processes, such as embryo development, cell differentiation, cell growth, metabolic coordination of avascular organs, and neural development [6]. Gap junction channels form polymorphic maculae or plaques with a few to thousands of units [4] and are composed of connexins in chordates and innexins in prechordates [7,8]. Vertebrates have innexin-related proteins, called pannexins, their roles in forming gap junctions are still under debate [9,10]

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