1. Javad Jamshidi Fasa University of Medical Sciences Proteins Into membranes and Organelles and Vesicular Traffic Moving

2. A typical mammalian cell contains up to 10,000 different kinds of proteins About half of the different kinds of proteins produced in a cell are delivered to various membrane-bounded organelles within the cell or to the cell surface The delivery of newly synthesized proteins to their proper cellular destinations, usually referred to as protein targeting or protein sorting

3. Two very different kinds of processes: signal-based targeting vesicle-based trafficking

5. Targeting of a newly synthesized protein from the cytoplasm to an intracellular organelle Targeting can occur during translation or soon after synthesis of the protein is complete Proteins are sorted to the endoplasmic reticulum (ER), mitochondria, chloroplasts, peroxisomes, and nucleus by this general process

6. Is known as the secretory pathway, and involves transport of proteins from the ER to their final destination within membrane-enclosed vesicles For many proteins, including in the outside of the cell and integral membrane proteins are transported to the Golgi, lysosome, and plasma membrane by this process The secretory pathway begins in the ER; thus all proteins slated to enter the secretory pathway are initially targeted to this organelle

8. How a given protein could be directed to only one specific membrane?? How relatively large hydrophilic protein molecules could be translocated across a hydrophobic membrane without disrupting the bilayer??

9. All soluble proteins that will eventually be secreted from the cell-as well as those destined for the lumen of the ER, Golgi, or lysosomes-are initially delivered to the ER lumen ER is the location where about one-third of the proteins in a typical cell fold into their native conformations Not all proteins that are targeted to the ER are actually secreted from the cell

10. A 16- to 30-residue ER signal sequence in the nascent protein directs the ribosome to the ER membrane An ER signal sequence typically is located at the N- terminus of the protein Contain one or more positively charged amino acids adjacent to a continuous stretch of 6-12 hydrophobic residues (known as the hydrophobic core-essential for their function) For most secretory proteins, the signal sequence is cleaved from the protein

11. A cytosolic ribnucleoprotein particle that transiently binds to both the ER signal sequence and large ribosomal subunit Targets the nascent protein-ribosome complex to the ER membrane by binding to the SRP receptor on the membrane The SRP is made up of six proteins bound to a 300- nucleotide RNA, which acts as a scaffold for the hexamer.

15. The topology,number of times that its polypeptide spans the membrane and the orientation of protein The key elements of a protein that determine its topology are membrane-spanning segments themselves, which usually are a helices containing 20-25 hydrophobic amino acids

16. Different Types of Transmembrane Proteins

19. Membrane and soluble secretory proteins synthesized on the rough ER undergo four principal modifications: 1. Covalent addition and processing of carbohydrates (glycosylation) in the ER and Golgi 2. Formation of disulfide bonds in the ER, 3. Proper folding of polypeptide chains and assembly of multisubunit proteins in the ER, 4. Specific proteolytic cleavages in the ER, Golgi, and secretory vesicles.

20. Amphipathic N-Terminal Signal Sequences Direct Proteins to the Mitochondrial Matrix located at the N-terminus, are usually 20-50 amino acids in length. Mitochondrial Protein Import Requires Outer- Membrane Receptors and Translocons in Both Membranes

24. Proteins imported to or exported from the nucleus contain a specific amino acid sequence that functions as a nuclear localization signal (NLS) or a nuclear- export signal (NES) A cargo protein bearing an NES or NLS trans locates through nuclear pores bound to its cognate nuclear transport protein.

27. Secretory pathway and the mechanisms of vesicular traffic that allow proteins to be secreted from the cell or delivered to the plasma membrane and the lysosome. The secretory pathway carries both soluble and membrane proteins from the ER to their final destination Transport of membrane and soluble proteins from one membrane-bounded compartment to another is mediated by transport vesicles

33. Protein Transport Through The Secretory Pathway

35. Mutants In 5 Stages In The Secretory Pathway