ADAMTS-family protease MIG-17 regulates synaptic allometry by modifying the extracellular matrix and modulating glia morphology during growth

Abstract

57Synapses are largely established during embryogenesis and maintained during 58 growth. The mechanisms that regulate synaptic allometry-the maintenance of 59 synaptic positions during growth-are largely unknown. We performed forward 60 genetic screens in C. elegans for synaptic allometry mutants and identified mig-61 17, a secreted metalloprotease of the conserved ADAMTS family. Through 62 proteomic mass spectrometry analyses, cell biological and genetic studies we 63 determined that MIG-17 is expressed by muscle cells to modulate glia location 64 and morphology. Glia are proximal to synapses, and the glial location and 65 morphology determine synaptic position during growth. Mig-17 regulates 66 synapse allometry by influencing epidermal-glia crosstalk through the 67 regulation of basement membrane proteins, including collagen type IV, SPARC 68 and fibulin. Our findings underscore the importance of glia location in the 69 maintenance of synaptic allometry, and uncover a muscle-epidermal-glia 70 signaling axis, mediated through the extracellular matrix, in the regulation of 71 glia morphology and synaptic positions during growth. 72 73 74 75 76 77 78 the level of identifying molecular factors necessary for maintaining synaptic 99 stability, density and morphology (Lin and Koleske, 2010;Luo et al.

Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding

“…To overcome these limitations, we extended our previous studies of endogenous mNG-tagged g-laminin, dystroglycan, and aand b-integrins (Jayadev et al, 2019;Naegeli et al, 2017) to complete a comprehensive assembly of endogenously tagged BM components with 17 tagged BM matrix components and 12 tagged receptors. In addition, this evolving collection includes type IV collagen tagged with the photoconvertible fluorophore mEos2 and two BM-localized ADAMTS proteases-ADAMTS9/GON-1 (this study) and MIG-17 (Ji et al, 2019). Importantly, most of these BM components have strong loss-of-function phenotypes, including embryonic or larval lethality (laminin, type IV collagen, spondin, papilin, teneurin, perlecan, SPARC, and integrin) and sterility or low brood size (fibulin, hemicentin, dystroglycan, and ADAMTS9) (Kawano et al, 2009;Kramer, 2005;Kramerova et al, 2000;Muriel et al, 2005;Trzebiatowska et al, 2008;Vogel and Hedgecock, 2001;Woo et al, 2008).…”

Cell-type-specific promoters for C. elegans glia

“…We can clearly observe the thin, branch-like posterior processes that wrap around the nerve ringa feature that distinguishes CEPsh glia from other glia of C. elegans (Figure 2(B)). The ability to visualize these fine details makes it possible to investigate the role of CEPsh glia in shaping neuronal connections in the central neuropil, or nerve ring (Col on-Ramos, Margeta, & Shen, 2007;Ji et al, 2019;Rapti, Li, Shan, Lu, & Shaham, 2017;Shao, Watanabe, Christensen, Jorgensen, & Col on-Ramos, 2013).…”

Cell-type-specific promoters for C. elegans glia

“…2B). The ability to visualize these fine details makes it possible to investigate the role of CEPsh glia in shaping neuronal connections in the central neuropil, or nerve ring (Colón-Ramos et al, 2007;Ji et al, 2019;Rapti et al, 2017;Shao et al, 2013).…”