The tubular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions. Two classes of the conserved ER membrane proteins, atlastins and lunapark, have been shown to reside at the three-way junctions so far and be involved in the generation and stabilization of the three-way junctions. In this study, we report TMCC3 (transmembrane and coiled-coil domain family 3), a member of the TEX28 family, as another ER membrane protein that resides at the three-way junctions in mammalian cells. When the TEX28 family members were transfected into U2OS cells, TMCC3 specifically localized at the three-way junctions in the peripheral ER. TMCC3 bound to atlastins through the C-terminal transmembrane domains. A TMCC3 mutant lacking the N-terminal coiled-coil domain abolished localization to the three-way junctions, suggesting that TMCC3 localized independently of binding to atlastins. TMCC3 knockdown caused a decrease in the number of three-way junctions and expansion of ER sheets, leading to a reduction of the tubular ER network in U2OS cells. The TMCC3 knockdown phenotype was partially rescued by the overexpression of atlastin-2, suggesting that TMCC3 knockdown would decrease the activity of atlastins. These results indicate that TMCC3 localizes at the three-way junctions for the proper tubular ER network.
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In this issue Curtino and Aon (pp. 3109–3124) review glycogen biology, beginning with the discoveries of proteoglycogen and glycogenin, through to current research and the important new questions which can be addressed in the future. The cover depicts pathways of de novo proteoglycogen biogenesis from glycogenin and proposed degradation via autophagy, along with the classical turnover route of the polysaccharide moiety. Image created by Marc Raley, Visual Media Services NIA IRP.
TMCC3 localizes at the three-way junctions for the proper tubular network of the endoplasmic reticulum
Sindhu Wisesa, Yasunori Yamamoto, Toshiaki Sakisaka; TMCC3 localizes at the three-way junctions for the proper tubular network of the endoplasmic reticulum. Biochem J 15 November 2019; 476 (21): 3241–3260. doi: https://doi.org/10.1042/BCJ20190359
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