The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. These studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure.


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Literature Cited

  1. Veratti E. 1.  1961. Investigations on the fine structure of striated muscle fiber read before the Reale Istituto Lombardo, 13 March 1902. J. Biophys. Biochem. Cytol. 10:Suppl. 41–59 [Google Scholar]
  2. Schuldiner M, Schwappach B. 2.  2013. From rags to riches—the history of the endoplasmic reticulum. Biochim. Biophys. Acta 1833:2389–91 [Google Scholar]
  3. Palade GE. 3.  1955. Studies on the endoplasmic reticulum. II. Simple dispositions in cells in situ. J. Biophys. Biochem. Cytol 1:56–7-82 [Google Scholar]
  4. Palade GE, Porter KR. 4.  1954. Studies on the endoplasmic reticulum. I. Its identification in cells in situ. J. Exp. Med 100:641–56 [Google Scholar]
  5. Porter KR, Palade GE. 5.  1957. Studies on the endoplasmic reticulum. III. Its form and distribution in striated muscle cells. J. Biophys. Biochem. Cytol 3:269–300 [Google Scholar]
  6. Mazzarello P, Calligaro A, Vannini V, Muscatello U. 6.  2003. The sarcoplasmic reticulum: its discovery and rediscovery. Nat. Rev. Mol. Cell Biol. 4:69–74 [Google Scholar]
  7. Hetzer MW, Walther TC, Mattaj IW. 7.  2005. Pushing the envelope: structure, function, and dynamics of the nuclear periphery. Annu. Rev. Cell Dev. Biol. 21:347–80 [Google Scholar]
  8. D'Angelo MA, Hetzer MW. 8.  2006. The role of the nuclear envelope in cellular organization. Cell Mol. Life Sci. 63:316–32 [Google Scholar]
  9. Burke B, Ellenberg J. 9.  2002. Remodelling the walls of the nucleus. Nat. Rev. Mol. Cell Biol. 3:487–97 [Google Scholar]
  10. Bernales S, McDonald KL, Walter P. 10.  2006. Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLOS Biol. 4:e423 [Google Scholar]
  11. West M, Zurek N, Hoenger A, Voeltz GK. 11.  2011. A 3D analysis of yeast ER structure reveals how ER domains are organized by membrane curvature. J. Cell Biol. 193:333–46 [Google Scholar]
  12. Friedman JR, Voeltz GK. 12.  2011. The ER in 3D: a multifunctional dynamic membrane network. Trends Cell Biol. 21:709–17 [Google Scholar]
  13. Shibata Y, Shemesh T, Prinz WA, Palazzo AF, Kozlov MM, Rapoport TA. 13.  2010. Mechanisms determining the morphology of the peripheral ER. Cell 143:774–88 [Google Scholar]
  14. Voeltz GK, Rolls MM, Rapoport TA. 14.  2002. Structural organization of the endoplasmic reticulum. EMBO Rep. 3:944–50 [Google Scholar]
  15. Shibata Y, Voeltz GK, Rapoport TA. 15.  2006. Rough sheets and smooth tubules. Cell 126:435–39 [Google Scholar]
  16. Terasaki M, Shemesh T, Kasthuri N, Klemm RW, Schalek R. 16.  et al. 2013. Stacked endoplasmic reticulum sheets are connected by helicoidal membrane motifs. Cell 154:285–96 [Google Scholar]
  17. Baumann O, Walz B. 17.  2001. Endoplasmic reticulum of animal cells and its organization into structural and functional domains. Int. Rev. Cytol. 205:149–214 [Google Scholar]
  18. Maxfield FR, McGraw TE. 18.  2004. Endocytic recycling. Nat. Rev. Mol. Cell Biol. 5:121–32 [Google Scholar]
  19. Mayor S, Presley JF, Maxfield FR. 19.  1993. Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process. J. Cell Biol. 121:1257–69 [Google Scholar]
  20. Dunn KW, McGraw TE, Maxfield FR. 20.  1989. Iterative fractionation of recycling receptors from lysosomally destined ligands in an early sorting endosome. J. Cell Biol. 109:3303–14 [Google Scholar]
  21. Zhang D, Vjestica A, Oliferenko S. 21.  2012. Plasma membrane tethering of the cortical ER necessitates its finely reticulated architecture. Curr. Biol. 22:2048–52 [Google Scholar]
  22. Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K. 22.  2000. Junctophilins: a novel family of junctional membrane complex proteins. Mol. Cell 6:11–22 [Google Scholar]
  23. Schneider MF. 23.  1994. Control of calcium release in functioning skeletal muscle fibers. Annu. Rev. Physiol. 56:463–84 [Google Scholar]
  24. Block BA, Imagawa T, Campbell KP, Franzini-Armstrong C. 24.  1988. Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle. J. Cell Biol. 107:2587–600 [Google Scholar]
  25. Franzini-Armstrong C. 25.  1970. Studies of the triad: I. Structure of the junction in frog twitch fibers. J. Cell Biol. 47:488–99 [Google Scholar]
  26. Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE. 26.  et al. 1998. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280:1763–66 [Google Scholar]
  27. Csordas G, Thomas AP, Hajnoczky G. 27.  1999. Quasi-synaptic calcium signal transmission between endoplasmic reticulum and mitochondria. EMBO J. 18:96–108 [Google Scholar]
  28. Luik RM, Wang B, Prakriya M, Wu MM, Lewis RS. 28.  2008. Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation. Nature 454:538–42 [Google Scholar]
  29. Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED. 29.  et al. 2009. STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1. Cell 136:876–90 [Google Scholar]
  30. Giordano F, Saheki Y, Idevall-Hagren O, Colombo SF, Pirruccello M. 30.  et al. 2013. PI4,5P2-dependent and Ca2+-regulated ER–PM interactions mediated by the extended synaptotagmins. Cell 153:1494–509 [Google Scholar]
  31. Chang CL, Hsieh TS, Yang TT, Rothberg KG, Azizoglu DB. 31.  et al. 2013. Feedback regulation of receptor-induced Ca2+ signaling mediated by E-Syt1 and Nir2 at endoplasmic reticulum–plasma membrane junctions. Cell Rep. 5:813–25 [Google Scholar]
  32. Terasaki M, Song J, Wong JR, Weiss MJ, Chen LB. 32.  1984. Localization of endoplasmic reticulum in living and glutaraldehyde-fixed cells with fluorescent dyes. Cell 38:101–8 [Google Scholar]
  33. Terasaki M, Chen LB, Fujiwara K. 33.  1986. Microtubules and the endoplasmic reticulum are highly interdependent structures. J. Cell Biol. 103:1557–68 [Google Scholar]
  34. Waterman-Storer CM, Salmon ED. 34.  1998. Endoplasmic reticulum membrane tubules are distributed by microtubules in living cells using three distinct mechanisms. Curr. Biol. 8:798–806 [Google Scholar]
  35. Bola B, Allan V. 35.  2009. How and why does the endoplasmic reticulum move?. Biochem. Soc. Trans. 37:961–65 [Google Scholar]
  36. Lee C, Chen LB. 36.  1988. Dynamic behavior of endoplasmic reticulum in living cells. Cell 54:37–46 [Google Scholar]
  37. Fehrenbacher KL, Davis D, Wu M, Boldogh I, Pon LA. 37.  2002. Endoplasmic reticulum dynamics, inheritance, and cytoskeletal interactions in budding yeast. Mol. Biol. Cell 13:854–65 [Google Scholar]
  38. Shibata Y, Voss C, Rist JM, Hu J, Rapoport TA. 38.  et al. 2008. The reticulon and DP1/Yop1p proteins form immobile oligomers in the tubular endoplasmic reticulum. J. Biol. Chem. 283:18892–904 [Google Scholar]
  39. Boevink P, Oparka K, Santa Cruz S, Martin B, Betteridge A, Hawes C. 39.  1998. Stacks on tracks: the plant Golgi apparatus traffics on an actin/ER network. Plant J. 15:441–47 [Google Scholar]
  40. Ueda H, Yokota E, Kutsuna N, Shimada T, Tamura K. 40.  et al. 2010. Myosin-dependent endoplasmic reticulum motility and F-actin organization in plant cells. PNAS 107:6894–99 [Google Scholar]
  41. Sanger JM, Dome JS, Mittal B, Somlyo AV, Sanger JW. 41.  1989. Dynamics of the endoplasmic reticulum in living non-muscle and muscle cells. Cell Motil. Cytoskelet. 13:301–19 [Google Scholar]
  42. Wang Y, Mattson MP, Furukawa K. 42.  2002. Endoplasmic reticulum calcium release is modulated by actin polymerization. J. Neurochem. 82:945–52 [Google Scholar]
  43. Wagner W, Brenowitz SD, Hammer JA 3rd. 43.  2011. Myosin-Va transports the endoplasmic reticulum into the dendritic spines of Purkinje neurons. Nat. Cell Biol. 13:40–48 [Google Scholar]
  44. Tabb JS, Molyneaux BJ, Cohen DL, Kuznetsov SA, Langford GM. 44.  1998. Transport of ER vesicles on actin filaments in neurons by myosin V. J. Cell Sci. 111:3221–34 [Google Scholar]
  45. Joensuu M, Belevich I, Ramo O, Nevzorov I, Vihinen H. 45.  et al. 2014. ER sheet persistence is coupled to myosin 1c–regulated dynamic actin filament arrays. Mol. Biol. Cell 25:1111–26 [Google Scholar]
  46. Friedman JR, Webster BM, Mastronarde DN, Verhey KJ, Voeltz GK. 46.  2010. ER sliding dynamics and ER–mitochondrial contacts occur on acetylated microtubules. J. Cell Biol. 190:363–75 [Google Scholar]
  47. Grigoriev I, Gouveia SM, van der Vaart B, Demmers J, Smyth JT. 47.  et al. 2008. STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER. Curr. Biol. 18:177–82 [Google Scholar]
  48. Feiguin F, Ferreira A, Kosik KS, Caceres A. 48.  1994. Kinesin-mediated organelle translocation revealed by specific cellular manipulations. J. Cell Biol. 127:1021–39 [Google Scholar]
  49. Wozniak MJ, Bola B, Brownhill K, Yang YC, Levakova V, Allan VJ. 49.  2009. Role of kinesin-1 and cytoplasmic dynein in endoplasmic reticulum movement in VERO cells. J. Cell Sci. 122:1979–89 [Google Scholar]
  50. Bannai H, Inoue T, Nakayama T, Hattori M, Mikoshiba K. 50.  2004. Kinesin dependent, rapid, bi-directional transport of ER sub-compartment in dendrites of hippocampal neurons. J. Cell Sci. 117:163–75 [Google Scholar]
  51. Wozniak MJ, Allan VJ. 51.  2006. Cargo selection by specific kinesin light chain 1 isoforms. EMBO J. 25:5457–68 [Google Scholar]
  52. Waterman-Storer CM, Gregory J, Parsons SF, Salmon ED. 52.  1995. Membrane/microtubule tip attachment complexes (TACs) allow the assembly dynamics of plus ends to push and pull membranes into tubulovesicular networks in interphase Xenopus egg extracts. J. Cell Biol. 130:1161–69 [Google Scholar]
  53. Pani B, Ong HL, Liu X, Rauser K, Ambudkar IS, Singh BB. 53.  2008. Lipid rafts determine clustering of STIM1 in endoplasmic reticulum–plasma membrane junctions and regulation of store-operated Ca2+ entry (SOCE). J. Biol. Chem. 283:17333–40 [Google Scholar]
  54. Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M. 54.  et al. 2005. STIM1, an essential and conserved component of store-operated Ca2+ channel function. J. Cell Biol. 169:435–45 [Google Scholar]
  55. Prinz WA, Grzyb L, Veenhuis M, Kahana JA, Silver PA, Rapoport TA. 55.  2000. Mutants affecting the structure of the cortical endoplasmic reticulum in Saccharomyces cerevisiae. J. Cell Biol. 150:461–74 [Google Scholar]
  56. Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK. 56.  2011. ER tubules mark sites of mitochondrial division. Science 334:358–62 [Google Scholar]
  57. Friedman JR, Dibenedetto JR, West M, Rowland AA, Voeltz GK. 57.  2013. Endoplasmic reticulum–endosome contact increases as endosomes traffic and mature. Mol. Biol. Cell 24:1030–40 [Google Scholar]
  58. Zajac AL, Goldman YE, Holzbaur EL, Ostap EM. 58.  2013. Local cytoskeletal and organelle interactions impact molecular-motor-driven early endosomal trafficking. Curr. Biol. 23:1173–80 [Google Scholar]
  59. Rowland AA, Chitwood PJ, Phillips MJ, Voeltz GK. 59.  2014. ER contact sites define the position and timing of endosome fission. Cell 159:1027–41 [Google Scholar]
  60. Oertle T, Klinger M, Stuermer CA, Schwab ME. 60.  2003. A reticular rhapsody: phylogenic evolution and nomenclature of the RTN/Nogo gene family. FASEB J. 17:1238–47 [Google Scholar]
  61. Di Sano F, Bernardoni P, Piacentini M. 61.  2012. The reticulons: guardians of the structure and function of the endoplasmic reticulum. Exp. Cell Res. 318:1201–7 [Google Scholar]
  62. Tolley N, Sparkes I, Craddock CP, Eastmond PJ, Runions J. 62.  et al. 2010. Transmembrane domain length is responsible for the ability of a plant reticulon to shape endoplasmic reticulum tubules in vivo. Plant J. 64:411–18 [Google Scholar]
  63. Roebroek AJ, Van de Velde HJ, Van Bokhoven A, Broers JL, Ramaekers FC, Van de Ven WJ. 63.  1993. Cloning and expression of alternative transcripts of a novel neuroendocrine-specific gene and identification of its 135-kDa translational product. J. Biol. Chem. 268:13439–47 [Google Scholar]
  64. Roebroek AJ, Ayoubi TA, Van de Velde HJ, Schoenmakers EF, Pauli IG, Van de Ven WJ. 64.  1996. Genomic organization of the human NSP gene, prototype of a novel gene family encoding reticulons. Genomics 32:191–99 [Google Scholar]
  65. Roebroek AJ, Contreras B, Pauli IG, Van de Ven WJ. 65.  1998. cDNA cloning, genomic organization, and expression of the human RTN2 gene, a member of a gene family encoding reticulons. Genomics 51:98–106 [Google Scholar]
  66. Moreira EF, Jaworski CJ, Rodriguez IR. 66.  1999. Cloning of a novel member of the reticulon gene family (RTN3): gene structure and chromosomal localization to 11q13. Genomics 58:73–81 [Google Scholar]
  67. GrandPré T, Nakamura F, Vartanian T, Strittmatter SM. 67.  2000. Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 403:439–44 [Google Scholar]
  68. Oertle T, Huber C, van der Putten H, Schwab ME. 68.  2003. Genomic structure and functional characterisation of the promoters of human and mouse nogo/rtn4. J. Mol. Biol. 325:299–323 [Google Scholar]
  69. Iwahashi J, Kawasaki I, Kohara Y, Gengyo-Ando K, Mitani S. 69.  et al. 2002. Caenorhabditis elegans reticulon interacts with RME-1 during embryogenesis. Biochem. Biophys. Res. Commun. 293:698–704 [Google Scholar]
  70. Voeltz GK, Prinz WA, Shibata Y, Rist JM, Rapoport TA. 70.  2006. A class of membrane proteins shaping the tubular endoplasmic reticulum. Cell 124:573–86 [Google Scholar]
  71. Tolley N, Sparkes IA, Hunter PR, Craddock CP, Nuttall J. 71.  et al. 2008. Overexpression of a plant reticulon remodels the lumen of the cortical endoplasmic reticulum but does not perturb protein transport. Traffic 9:94–102 [Google Scholar]
  72. Yang YS, Strittmatter SM. 72.  2007. The reticulons: a family of proteins with diverse functions. Genome Biol. 8:234 [Google Scholar]
  73. Lin S, Sun S, Hu J. 73.  2012. Molecular basis for sculpting the endoplasmic reticulum membrane. Int. J. Biochem. Cell Biol. 44:1436–43 [Google Scholar]
  74. Zurek N, Sparks L, Voeltz G. 74.  2011. Reticulon short hairpin transmembrane domains are used to shape ER tubules. Traffic 12:28–41 [Google Scholar]
  75. Iwahashi J, Hamada N, Watanabe H. 75.  2007. Two hydrophobic segments of the RTN1 family determine the ER localization and retention. Biochem. Biophys. Res. Commun. 355:508–12 [Google Scholar]
  76. Wakana Y, Koyama S, Nakajima K, Hatsuzawa K, Nagahama M. 76.  et al. 2005. Reticulon 3 is involved in membrane trafficking between the endoplasmic reticulum and Golgi. Biochem. Biophys. Res. Commun. 334:1198–205 [Google Scholar]
  77. Liu Y, Vidensky S, Ruggiero AM, Maier S, Sitte HH, Rothstein JD. 77.  2008. Reticulon RTN2B regulates trafficking and function of neuronal glutamate transporter EAAC1. J. Biol. Chem. 283:6561–71 [Google Scholar]
  78. Steiner P, Kulangara K, Sarria JC, Glauser L, Regazzi R, Hirling H. 78.  2004. Reticulon 1C/neuroendocrine-specific protein C interacts with SNARE proteins. J. Neurochem. 89:569–80 [Google Scholar]
  79. Hu J, Shibata Y, Voss C, Shemesh T, Li Z. 79.  et al. 2008. Membrane proteins of the endoplasmic reticulum induce high-curvature tubules. Science 319:1247–50 [Google Scholar]
  80. Puhka M, Vihinen H, Joensuu M, Jokitalo E. 80.  2007. Endoplasmic reticulum remains continuous and undergoes sheet-to-tubule transformation during cell division in mammalian cells. J. Cell Biol. 179:895–909 [Google Scholar]
  81. Rolls MM, Hall DH, Victor M, Stelzer EH, Rapoport TA. 81.  2002. Targeting of rough endoplasmic reticulum membrane proteins and ribosomes in invertebrate neurons. Mol. Biol. Cell 13:1778–91 [Google Scholar]
  82. Schweizer A, Ericsson M, Bachi T, Griffiths G, Hauri HP. 82.  1993. Characterization of a novel 63 kDa membrane protein. Implications for the organization of the ER-to-Golgi pathway. J. Cell Sci. 104:671–83 [Google Scholar]
  83. Klopfenstein DR, Klumperman J, Lustig A, Kammerer RA, Oorschot V, Hauri HP. 83.  2001. Subdomain-specific localization of CLIMP-63 (p63) in the endoplasmic reticulum is mediated by its luminal α-helical segment. J. Cell Biol. 153:1287–300 [Google Scholar]
  84. Schweizer A, Rohrer J, Slot JW, Geuze HJ, Kornfeld S. 84.  1995. Reassessment of the subcellular localization of p63. J. Cell Sci. 108:Part 62477–85 [Google Scholar]
  85. Klopfenstein DR, Kappeler F, Hauri HP. 85.  1998. A novel direct interaction of endoplasmic reticulum with microtubules. EMBO J. 17:6168–77 [Google Scholar]
  86. Orso G, Pendin D, Liu S, Tosetto J, Moss TJ. 86.  et al. 2009. Homotypic fusion of ER membranes requires the dynamin-like GTPase atlastin. Nature 460:978–83 [Google Scholar]
  87. Hu J, Shibata Y, Zhu PP, Voss C, Rismanchi N. 87.  et al. 2009. A class of dynamin-like GTPases involved in the generation of the tubular ER network. Cell 138:549–61 [Google Scholar]
  88. Zhu PP, Patterson A, Lavoie B, Stadler J, Shoeb M. 88.  et al. 2003. Cellular localization, oligomerization, and membrane association of the hereditary spastic paraplegia 3A (SPG3A) protein atlastin. J. Biol. Chem. 278:49063–71 [Google Scholar]
  89. Chan DC. 89.  2006. Mitochondrial fusion and fission in mammals. Annu. Rev. Cell Dev. Biol. 22:79–99 [Google Scholar]
  90. Byrnes LJ, Singh A, Szeto K, Benvin NM, O'Donnell JP. 90.  et al. 2013. Structural basis for conformational switching and GTP loading of the large G protein atlastin. EMBO J. 32:369–84 [Google Scholar]
  91. Bian X, Klemm RW, Liu TY, Zhang M, Sun S. 91.  et al. 2011. Structures of the atlastin GTPase provide insight into homotypic fusion of endoplasmic reticulum membranes. PNAS 108:3976–81 [Google Scholar]
  92. Byrnes LJ, Sondermann H. 92.  2011. Structural basis for the nucleotide-dependent dimerization of the large G protein atlastin-1/SPG3A. PNAS 108:2216–21 [Google Scholar]
  93. Pendin D, Tosetto J, Moss TJ, Andreazza C, Moro S. 93.  et al. 2011. GTP-dependent packing of a three-helix bundle is required for atlastin-mediated fusion. PNAS 108:16283–88 [Google Scholar]
  94. Goyal U, Blackstone C. 94.  2013. Untangling the web: mechanisms underlying ER network formation. Biochim. Biophys. Acta 1833:2492–98 [Google Scholar]
  95. Moss TJ, Andreazza C, Verma A, Daga A, McNew JA. 95.  2011. Membrane fusion by the GTPase atlastin requires a conserved C-terminal cytoplasmic tail and dimerization through the middle domain. PNAS 108:11133–38 [Google Scholar]
  96. Liu TY, Bian X, Sun S, Hu X, Klemm RW. 96.  et al. 2012. Lipid interaction of the C terminus and association of the transmembrane segments facilitate atlastin-mediated homotypic endoplasmic reticulum fusion. PNAS 109:e2146–54 [Google Scholar]
  97. English AR, Voeltz GK. 97.  2013. Endoplasmic reticulum structure and interconnections with other organelles. Cold Spring Harb. Perspect. Biol. 5:a013227 [Google Scholar]
  98. Anwar K, Klemm RW, Condon A, Severin KN, Zhang M. 98.  et al. 2012. The dynamin-like GTPase Sey1p mediates homotypic ER fusion in S. cerevisiae. J. Cell Biol. 197:209–17 [Google Scholar]
  99. Chen S, Novick P, Ferro-Novick S. 99.  2012. ER network formation requires a balance of the dynamin-like GTPase Sey1p and the Lunapark family member Lnp1p. Nat. Cell Biol. 14:707–16 [Google Scholar]
  100. Chen S, Novick P, Ferro-Novick S. 100.  2013. ER structure and function. Curr. Opin. Cell Biol. 25:428–33 [Google Scholar]
  101. English AR, Voeltz GK. 101.  2013. Rab10 GTPase regulates ER dynamics and morphology. Nat. Cell Biol. 15:169–78 [Google Scholar]
  102. Gerondopoulos A, Bastos RN, Yoshimura S, Anderson R, Carpanini S. 102.  et al. 2014. Rab18 and a Rab18 GEF complex are required for normal ER structure. J. Cell Biol. 205:707–20 [Google Scholar]
  103. Renvoise B, Blackstone C. 103.  2010. Emerging themes of ER organization in the development and maintenance of axons. Curr. Opin. Neurobiol. 20:531–37 [Google Scholar]
  104. Cui-Wang T, Hanus C, Cui T, Helton T, Bourne J. 104.  et al. 2012. Local zones of endoplasmic reticulum complexity confine cargo in neuronal dendrites. Cell 148:309–21 [Google Scholar]
  105. Terasaki M, Slater NT, Fein A, Schmidek A, Reese TS. 105.  1994. Continuous network of endoplasmic reticulum in cerebellar Purkinje neurons. PNAS 91:7510–14 [Google Scholar]
  106. Spacek J, Harris KM. 106.  1997. Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. J. Neurosci. 17:190–203 [Google Scholar]
  107. Goldberg JL. 107.  2003. How does an axon grow?. Genes Dev. 17:941–58 [Google Scholar]
  108. Placido AI, Pereira CM, Duarte AI, Candeias E, Correia SC. 108.  et al. 2014. The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: Implications for Alzheimer's disease. Biochim. Biophys. Acta 1842:1444–53 [Google Scholar]
  109. Chiurchiu V, Maccarrone M, Orlacchio A. 109.  2014. The role of reticulons in neurodegenerative diseases. Neuromol. Med. 16:3–15 [Google Scholar]
  110. He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R. 110.  2004. Reticulon family members modulate BACE1 activity and amyloid-β peptide generation. Nat. Med. 10:959–65 [Google Scholar]
  111. Schon EA, Area-Gomez E. 111.  2013. Mitochondria-associated ER membranes in Alzheimer disease. Mol. Cell Neurosci. 55:26–36 [Google Scholar]
  112. Fraser T, Tayler H, Love S. 112.  2010. Fatty acid composition of frontal, temporal and parietal neocortex in the normal human brain and in Alzheimer's disease. Neurochem. Res. 35:503–13 [Google Scholar]
  113. Pettegrew JW, Panchalingam K, Hamilton RL, McClure RJ. 113.  2001. Brain membrane phospholipid alterations in Alzheimer's disease. Neurochem. Res. 26:771–82 [Google Scholar]
  114. Gillardon F, Rist W, Kussmaul L, Vogel J, Berg M. 114.  et al. 2007. Proteomic and functional alterations in brain mitochondria from Tg2576 mice occur before amyloid plaque deposition. Proteomics 7:605–16 [Google Scholar]
  115. Wang X, Su B, Zheng L, Perry G, Smith MA, Zhu X. 115.  2009. The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease. J. Neurochem. 109:Suppl. 1153–59 [Google Scholar]
  116. Hedskog L, Pinho CM, Filadi R, Ronnback A, Hertwig L. 116.  et al. 2013. Modulation of the endoplasmic reticulum–mitochondria interface in Alzheimer's disease and related models. PNAS 110:7916–21 [Google Scholar]
  117. Area-Gomez E, del Carmen Lara Castillo M, Tambini MD, Guardia-Laguarta C, de Groof AJC. 117.  et al. 2012. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 31:4106–23 [Google Scholar]
  118. Winkler E, Kamp F, Scheuring J, Ebke A, Fukumori A, Steiner H. 118.  2012. Generation of Alzheimer disease–associated amyloid β42/43 peptide by γ-secretase can be inhibited directly by modulation of membrane thickness. J. Biol. Chem. 287:21326–34 [Google Scholar]
  119. Schumacher MM, Choi JY, Voelker DR. 119.  2002. Phosphatidylserine transport to the mitochondria is regulated by ubiquitination. J. Biol. Chem. 277:51033–42 [Google Scholar]
  120. Rusinol AE, Cui Z, Chen MH, Vance JE. 120.  1994. A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins. J. Biol. Chem. 269:27494–502 [Google Scholar]
  121. Blackstone C. 121.  2012. Cellular pathways of hereditary spastic paraplegia. Annu. Rev. Neurosci. 35:25–47 [Google Scholar]
  122. Park SH, Blackstone C. 122.  2010. Further assembly required: construction and dynamics of the endoplasmic reticulum network. EMBO Rep. 11:515–21 [Google Scholar]
  123. McCorquodale DS 3rd, Ozomaro U, Huang J, Montenegro G, Kushman A. 123.  et al. 2011. Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia. Clin. Genet. 79:523–30 [Google Scholar]
  124. Salinas S, Proukakis C, Crosby A, Warner TT. 124.  2008. Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol. 7:1127–38 [Google Scholar]
  125. Rismanchi N, Soderblom C, Stadler J, Zhu PP, Blackstone C. 125.  2008. Atlastin GTPases are required for Golgi apparatus and ER morphogenesis. Hum. Mol. Genet. 17:1591–604 [Google Scholar]
  126. Zhu PP, Soderblom C, Tao-Cheng JH, Stadler J, Blackstone C. 126.  2006. SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development. Hum. Mol. Genet. 15:1343–53 [Google Scholar]
  127. Wang T, Liu Y, Xu XH, Deng CY, Wu KY. 127.  et al. 2011. Lgl1 activation of rab10 promotes axonal membrane trafficking underlying neuronal polarization. Dev. Cell 21:431–44 [Google Scholar]
  128. Zuchner S, Wang G, Tran-Viet KN, Nance MA, Gaskell PC. 128.  et al. 2006. Mutations in the novel mitochondrial protein REEP1 cause hereditary spastic paraplegia type 31. Am. J. Hum. Genet. 79:365–69 [Google Scholar]
  129. Saito H, Kubota M, Roberts RW, Chi Q, Matsunami H. 129.  2004. RTP family members induce functional expression of mammalian odorant receptors. Cell 119:679–91 [Google Scholar]
  130. Beetz C, Koch N, Khundadze M, Zimmer G, Nietzsche S. 130.  et al. 2013. A spastic paraplegia mouse model reveals REEP1-dependent ER shaping. J. Clin. Investig. 123:4273–82 [Google Scholar]
  131. Evans K, Keller C, Pavur K, Glasgow K, Conn B, Lauring B. 131.  2006. Interaction of two hereditary spastic paraplegia gene products, spastin and atlastin, suggests a common pathway for axonal maintenance. PNAS 103:10666–71 [Google Scholar]
  132. Sanderson CM, Connell JW, Edwards TL, Bright NA, Duley S. 132.  et al. 2006. Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners. Hum. Mol. Genet. 15:307–18 [Google Scholar]
  133. El-Hage N, Luo G. 133.  2003. Replication of hepatitis C virus RNA occurs in a membrane-bound replication complex containing nonstructural viral proteins and RNA. J. Gen. Virol. 84:2761–69 [Google Scholar]
  134. Gosert R, Egger D, Lohmann V, Bartenschlager R, Blum HE. 134.  et al. 2003. Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J. Virol. 77:5487–92 [Google Scholar]
  135. Mackenzie JM, Jones MK, Young PR. 135.  1996. Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication. Virology 220:232–40 [Google Scholar]
  136. Knoops K, Kikkert M, Worm SH, Zevenhoven-Dobbe JC, van der Meer Y. 136.  et al. 2008. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLOS Biol. 6:e226 [Google Scholar]
  137. Schwartz M, Chen J, Janda M, Sullivan M, den Boon J, Ahlquist P. 137.  2002. A positive-strand RNA virus replication complex parallels form and function of retrovirus capsids. Mol. Cell 9:505–14 [Google Scholar]
  138. Bamunusinghe D, Seo JK, Rao AL. 138.  2011. Subcellular localization and rearrangement of endoplasmic reticulum by brome mosaic virus capsid protein. J. Virol. 85:2953–63 [Google Scholar]
  139. Su HL, Liao CL, Lin YL. 139.  2002. Japanese encephalitis virus infection initiates endoplasmic reticulum stress and an unfolded protein response. J. Virol. 76:4162–71 [Google Scholar]
  140. Egger D, Wolk B, Gosert R, Bianchi L, Blum HE. 140.  et al. 2002. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J. Virol. 76:5974–84 [Google Scholar]
  141. Welsch S, Miller S, Romero-Brey I, Merz A, Bleck CK. 141.  et al. 2009. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5:365–75 [Google Scholar]
  142. den Boon JA, Ahlquist P. 142.  2010. Organelle-like membrane compartmentalization of positive-strand RNA virus replication factories. Annu. Rev. Microbiol. 64:241–56 [Google Scholar]
  143. Diaz A, Wang X, Ahlquist P. 143.  2010. Membrane-shaping host reticulon proteins play crucial roles in viral RNA replication compartment formation and function. PNAS 107:16291–96 [Google Scholar]
  144. Diaz A, Ahlquist P. 144.  2012. Role of host reticulon proteins in rearranging membranes for positive-strand RNA virus replication. Curr. Opin. Microbiol. 15:519–24 [Google Scholar]
  145. Tang WF, Yang SY, Wu BW, Jheng JR, Chen YL. 145.  et al. 2007. Reticulon 3 binds the 2C protein of enterovirus 71 and is required for viral replication. J. Biol. Chem. 282:5888–98 [Google Scholar]
  146. Wu MJ, Ke PY, Hsu JT, Yeh CT, Horng JT. 146.  2014. Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates viral replication by disrupting NS4B self-interaction. Cell Microbiol. 16:1603–18 [Google Scholar]
  147. Hugle T, Fehrmann F, Bieck E, Kohara M, Krausslich HG. 147.  et al. 2001. The hepatitis C virus nonstructural protein 4B is an integral endoplasmic reticulum membrane protein. Virology 284:70–81 [Google Scholar]
  148. Gretton SN, Taylor AI, McLauchlan J. 148.  2005. Mobility of the hepatitis C virus NS4B protein on the endoplasmic reticulum membrane and membrane-associated foci. J. Gen. Virol. 86:1415–21 [Google Scholar]
  149. Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier MJ. 149.  2013. Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles. mBio 4:e00524–13 [Google Scholar]

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