ER and Golgi - Slides 080524 PDF

Organelles: Part 2: The Endoplasmic reticulum and The Golgi  are enrolled University.  Organelles– part 2 The Endoplasmic reticulum and the Golgi LO: Understand the main role of the endoplasmic reticulum (ER) Understand the main role of the Golgi Proteins destin...

Organelles: Part 2: The Endoplasmic reticulum and The Golgi  are enrolled University.  Organelles– part 2 The Endoplasmic reticulum and the Golgi LO: Understand the main role of the endoplasmic reticulum (ER) Understand the main role of the Golgi Proteins destined for secretion to the extracellular space or to the plasma membrane are imported, folded and transported through the ER Cell Biology Figure 20.4  OVERVIEW OF THE ENDOPLASMIC RETICULUM (ER) Cell Biology Figure 20.2 Electron micrograph Rough ER: Protein translocation, folding and modification Smooth ER: lipid metabolism, calcium release Protein synthesis directly into the lumen of the rough ER Cell Biology Figure 20.6 Schematic overview of the mammalian SRP bound to the signal sequence carrying 80S ribosome (RNC) based on a cryo-EM structure17 The SRP core (SRP54 and SRP RNA helix 8) as part of the S domain is positioned near the exit of the protein tunnel of the large ribosomal subunit. The 40S and 60S ribosomal subunits are yellow and gray, respectively. The SRP RNA is red and the SRP proteins are labeled as follows: SRP54NG, turquoise; SRP54M, dark blue; signal sequence, green; SRP19 and SRP68/72, pink; SRP9, turquoise; SRP14, dark blue. Peptidyl-tRNA (p-tRNA) between the ribosomal subunits and the nascent chain in the exit tunnel are labeled. Reference: Wild K, Halic M, Sinning I, Beckmann R. SRP meets the ribosome. Nat Struct Mol Biol. 2004 Nov;11(11):1049-53. doi: 10.1038/nsmb853. PMID: 15523481.  Schematic overview of cotranslational targeting of proteins destined for secretion or membrane insertion by SRP system Step I SRP interacts with the signal sequence as soon as it emerges from the ribosomal polypeptide exit tunnel Step II Peptide elongation stops upon formation of the RNC complex SRP–ribosome nascent chain complex (RNC complex), and the complex is targeted to the ER membrane by the interaction with the SRP signal receptor (SR) GTP binding to SRP and SR (requires energy) have been shown to be a prerequisite for formation of the SRP–SR complex. Step III The RNC is then transferred to the protein- conducting channel in the membrane (the translocon) and triggered by GTP hydrolysis in SRP and SR Reference: Wild K, Halic M, Sinning I, Beckmann R. SRP meets the ribosome. Nat Struct Mol Biol. 2004 Nov;11(11):1049-53. doi: 10.1038/nsmb853. PMID: 15523481. Step IV The SRP–SR complex dissociates Oligosaccharides are added to proteins in the ER Asparagine linked glycosylation is a common protein modification N-linked oligosaccharides are transferred to nascent proteins oligosaccharyltransferase (OST) ER enzymes (glucosidase and mannosidase) generate a series of glycan trimming intermediates that lectins in the ER recognise specifically and direct the Cell Biology Figure 20.11 nascent protein into various pathways: Polar oligosaccharides make proteins more hydrophilic and less protein folding (CRT/CNX cycle) likely to aggregate (clump). protein degradation (ERAD) protein export (via ERG1C53, By avoiding aggregation, the protein has a higher probability of VIP36 and VIPL) folding correctly. Protein maturation in the ER Folding and assembly factors such as calreticulin and calnexin (CRT/CNX cycle) interact with proteins throughout their lifetimes in the ER. Disulfide bond formation on cysteines and oligomerization direct correct protein folding. Reference: Cherepanova N, Shrimal S, Gilmore R. N-linked glycosylation and homeostasis of the endoplasmic reticulum. Curr Opin Cell Biol. 2016 Aug;41:57-65. doi: 10.1016/j.ceb.2016.03.021. Epub 2016 Apr 14. PMID: 27085638; PMCID: PMC4983500. Improperly folded proteins: Incorrectly assembled proteins are degraded, a process termed ER- associated degradation (ERAD), prevents accumulation of unsalvageable, misfolded proteins in the ER. Misfolded glycoproteins are transported across the ER membrane to the cytoplasm and then degraded.  The Golgi Apparatus Primary functions of the Golgi apparatus: 1: Complex chains of carbohydrates are added to proteins in the Golgi, in preparation for their biological functions at the cell surface. 2: The Golgi apparatus is a protein-sorting station for the delivery Cell Biology Figure 21.1 to many cellular destinations. Golgi resident proteins and membrane trafficking pathway Newly synthesized proteins enter the ER and are sorted into budding vesicles that are dependent on the Coat Protein Complex II (COPII). Vesicles move to the ER-Golgi intermediate compartment (ERGIC) and forward to the cis-Golgi networks (CGN) and the trans-Golgi cisternae. Finally, vesicles reach the trans-Golgi networks (TGN) and cargos sort to their final destinations such as: lysosomes Reference: Liu, J., Huang, Y., Li, T., Jiang, Z., Zeng, L., & Hu, Z. (2021). The role of the Golgi apparatus in endosomes disease (Review). International Journal of Molecular Medicine, 47, 38. https://doi.org/10.3892/ijmm.2021.4871 or the plasma membrane The Golgi apparatus Cell Biology Figure 21.18  The Golgi apparatus disassembles during cell division Cell Biology Figure 21.21 Complex chains of carbohydrates are added to proteins in the Golgi. A primary function of the Golgi apparatus is the glycosylation (ie, sugar modification) of proteins called glycoproteins Most cell-surface proteins and secreted proteins are glycosylated. Their glycans participate in numerous biological functions, including cell–cell and cell–matrix interactions, intracellular and intercellular trafficking, and signaling. The Golgi apparatus is a protein-sorting station for the delivery to many cellular destinations. 2: The Golgi apparatus is a protein-sorting station for the delivery to many cellular destinations. This includes transport to the plasma membrane, secretion to the cell exterior, sorting to the endosome/lysosomal system, or retrieval back to the ER. Cell Biology Figure 21.23  CONNECT 0 /flindersunlversity O@flinders ® @flindersu niversity CD)school/f Iinders-university/ O@flindersuniversity l=linders University a c k nowled ges the Traditional Own ers a n d Custodians of the lands ,on which its c a m pus es a re located , t h es e a re t h e Traditional Lands of the Arremte, Dagoma111 First !Nations of the South East, First Peoples of the River Murray & Mallee region, J a w o yn , K a u r n a , h r r a k i a , Ngadjuri, Ngarrindje i, Ramindjeri, Wa ru m u n gu , Wardaman and Yolngu people. W e honour their Elders past, pres,ent and emerging. rl.·. Flinders Flinders.edu.au University