TY - JOUR TI - Efficient protein targeting to the inner nuclear membrane requires Atlastin-dependent maintenance of ER topology AU - Pawar, Sumit AU - Ungricht, Rosemarie AU - Tiefenboeck, Peter AU - Leroux, Jean-Christophe AU - Kutay, Ulrike A2 - Schekman, Randy VL - 6 PY - 2017 DA - 2017/08/14 SP - e28202 C1 - eLife 2017;6:e28202 DO - 10.7554/eLife.28202 UR - https://doi.org/10.7554/eLife.28202 AB - Newly synthesized membrane proteins are targeted to the inner nuclear membrane (INM) by diffusion within the membrane system of the endoplasmic reticulum (ER), translocation through nuclear pore complexes (NPCs) and retention on nuclear partners. Using a visual in vitro assay we previously showed that efficient protein targeting to the INM depends on nucleotide hydrolysis. We now reveal that INM targeting is GTP-dependent. Exploiting in vitro reconstitution and in vivo analysis of INM targeting, we establish that Atlastins, membrane-bound GTPases of the ER, sustain the efficient targeting of proteins to the INM by their continued activity in preserving ER topology. When ER topology is altered, the long-range diffusional exchange of proteins in the ER network and targeting efficiency to the INM are diminished. Highlighting the general importance of proper ER topology, we show that Atlastins also influence NPC biogenesis and timely exit of secretory cargo from the ER. KW - inner nuclear membrane KW - ER KW - membrane protein KW - nuclear envelope KW - atlastin KW - GTPase JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -