The Endomenbrane System This system applies to cell surface proteins proteins excreted from the cell proteins that belong inside of or on the membrane of lysosomes golgi bodies or endoplasmic reticulum including enzymes and transporter proteins 1 Learning goal Students will understand some examples of where macromolecules in the cell originate and how they reach their final destinations Focus proteins how to distinguish which are translated into cytoplasm and which are translated into ER signals and receptors to direct proteins to final destinations 2 Cells use signals and receptors to sort proteins General rules The signal structure varies The receptor is always a protein The system depends on having the correct signal and the correct receptor Breaking either the signal or the receptor will make the shipped protein nonfunctional not because the protein doesn t work but because it doesn t reach its destination in the cell 3 Proteins destined for the nucleus the mitochondria or the peroxisome are translated into the cytoplasm then shipped to their destination mRNA NLS No signal remains in cytoplasm MTS PTS Ship to nucleus Ship to mitochondria Ship to peroxisome A subset of proteins are partially translated then complete translation into the rough ER ER specific signal mRNA These proteins are destined for 1 Secretion from the cell secretory proteins 2 Cell membrane surface proteins transporters receptors cell cell adhesion proteins 3 Golgi ER or lysosome either inside or on the membranes of these organelles Rough E R lumen The secretory pathway signal peptide is 5 30 hydrophobic amino acids at the Nterminus of the protein Often preceded by a basic amino acid or two 6 The signal peptide receptor is a pair of proteins SRP and SRPR SRP binds to SRP receptor SRP SRP comes off transcription res 1 rough ER lumen interior 2 rough ER membrane for me Once the translation is complete Signal recognition peptide binds to signal halts transcription moves ribosomes to rough ER membrane Once the translation into the ER or RER membrane is complete the signal peptide sequence is cleaved The resulting polypeptide is now shorter and may not begin with M 8 All proteins that go through this pathway have the signal peptide encoded in their DNA Figure 7 26 9 Proteins destined for secretion membranes or secretory pathway organelles complete their translation into the RER mRNA SP Translated into RER SP removed KDEL KK x x These proteins STAY in the RER The rest will be sent to the golgi bodies The proteins in the RER are checked for proper folding and then glycosylation is added to an arginine N linked This protein is ready to be shipped to the golgi apparatus Membranes can bud off and form vesicles that carry proteins This includes proteins embedded in the membranes cytoplasm ER lumen Vesicle contents NEVER mix with the cytoplasm The golgi apparatus is a series of stacked membranes with a receiving end and a shipping end Each stack has different enzymes which modify proteins in various ways Proteins destined for secretion membranes or secretory pathway organelles complete their translation into the RER mRNA SP Translated into RER SP removed KDEL Transported to golgi apparatus KK x x These proteins STAY in the RER M 6 P Shipped to lysosomes These proteins STAY in the golgi Shipped by vesicle to the cell membrane Golgi enzymes attach a phosphate group to the oligosaccharides on proteins destined for the lysosome M 6 P tagged protein What does the 6 stand for it s attached to carbon 6 Manose 6 phosphate signal tag added by Golgi enzymes M6PR is itself a signal with another receptor M6PRR on lysosomal membrane Figure 7 22 Mannose 6 phosphate receptor M6PR proteins on Golgi trans membrane You should be able to Describe the flow of information between RER golgi and cell membrane and other organelles Understand budding Understand why the lumens of these organelles never mix with the cytoplasm but can and do mix with the extracellular fluid Describe the journey of a secreted protein from gene to mRNA to creation in the RER to Golgi to Cell membrane How does a cell know this protein is going to be secreted Describe the journey of a lysosomal enzyme from gene to protein and why it goes to a lysosome instead of being shipped outside How does the golgi sort different proteins How does the signal work What is a receptor protein 17 You should be able to Understand and answer application questions about the processes as shown in figures 7 19 7 20 7 21 and 7 22 In these figures predict what will happen to proteins if key components of the process are missing or altered If given a protein and its ultimate destination predict whether It has an ER signal peptide tag in its primary amino acid sequence It will be glycossylated with carbohydrate signals It will go through the endomembrane system or be translated directly into the cytoplasm 18