Molecular Biology of the Cell Chapter 12 - Intracellular Compartments and Protein Sorting PDF

Molecular Biology of the Cell Sixth Edition Chapter 12 Intracellular Compartments and Protein Sorting  CHAPTER CONTENTS THE COMPARTMENTALIZATION OF CELLS THE TRANSPORT OF MOLECULES BETWEEN THE NUCLEUS AND THE CYTOSOL THE TRANSPORT OF PROTEINS INTO MITO...

Molecular Biology of the Cell Sixth Edition Chapter 12 Intracellular Compartments and Protein Sorting  CHAPTER CONTENTS THE COMPARTMENTALIZATION OF CELLS THE TRANSPORT OF MOLECULES BETWEEN THE NUCLEUS AND THE CYTOSOL THE TRANSPORT OF PROTEINS INTO MITOCHONDRIA AND CHLOROPLASTS PEROXISOMES THE ENDOPLASMIC RETICULUM THE TRANSPORT OF MOLECULES BETWEEN THE NUCLEUS AND THE CYTOSOL Introduction – Nuclear envelope (figure 7) THE TRANSPORT OF MOLECULES BETWEEN THE NUCLEUS AND THE CYTOSOL Introduction – Nuclear envelope (figure 7) – Inner membrane contains proteins that act as binding sites for chromosomes and for the nuclear lamina, a protein meshwork that provides structural support for the nuclear envelope – Outer membrane, which is continuous with the membrane of the ER. Like the ER membrane, the outer nuclear membrane is studded with ribosomes – Bidirectional traffic cytosol>nucleus : ? histones DNA polymerase , RNA , Rolymerase transcriptional regulator , , RNA processing protein RNA (m , r t, mi , , sn) THE TRANSPORT OF MOLECULES BETWEEN THE NUCLEUS AND THE CYTOSOL Nuclear Import Receptors Bind to Both Nuclear Localization Signals and NPC Proteins – Nuclear import receptors bind and transport specific cargo proteins containing the appropriate NLS (figure 11) V nuclear pore complexes Nuclear Import Receptors Bind to Both Nuclear Localization Signals and NPC Proteins I only exposed when loaded w, a cargo protein THE TRANSPORT OF MOLECULES BETWEEN THE NUCLEUS AND THE CYTOSOL Imonomer) The Ran GTPase Imposes Directionality on Transport Through NPCs – (figures 12~13) The Ran GTPase Imposes Directionality on Transport Through NPCs GTPase-activating proteins : activate GTPase Guanine nucleotide (GTP-GDP) exchange factor The Ran GTPase Imposes Directionality on Transport Through NPCs  THE ENDOPLASMIC RETICULUM Introduction – ER membrane is the site of production of all transmembrane proteins and lipids for most of the cell’s organelles. – Almost all of the proteins that will be secreted to the cell exterior are initially delivered to the ER lumen  THE ENDOPLASMIC RETICULUM Signal Sequences Were First Discovered in Proteins Imported into the Rough ER – The ER captures (two types of) selected proteins from the cytosol as they are being synthesized – Transmembrane proteins: function in the ER or destined to reside in the plasma membrane or the membrane of other organelles – Water-soluble proteins: fully released into the ER lumen and destined either for secretion or residence in the lumen of the ER or other organelles Signal Sequences Were First Discovered in Proteins Imported into the Rough ER (open when ribosome bound) cleave  A Signal-Recognition Particle (SRP) Directs the ER Signal Sequence to a Specific Receptor in the Rough ER Membrane ① so ④ dis Er ② SRP direct z ③  THE ENDOPLASMIC RETICULUM In Single-Pass Transmembrane Proteins, a Single Internal ER Signal Sequence Remains in the Lipid Bilayer as a Membrane-spanning a Helix – ER signal sequence is recognized twice: first by an SRP in the cytosol and then by a binding site in the pore of the protein translocator, where it serves as a start-transfer signal that opens the pore (see figure 35 for soluble proteins) – For transmembrane proteins, an additional signal segment stops the transfer process (stop-transfer signal) (figure 42,44) In Single-Pass Transmembrane Proteins, a Single Internal ER Signal Sequence Remains in the Lipid Bilayer as a Membrane-spanning a Helix anchor protein to membrane M I g Combinations of Start-Transfer and Stop-Transfer Signals Determine the Topology of Multipass Transmembrane Proteins  Oligosaccharides Are Used as Tags to Mark the State of Protein Folding Oligosaccharides Are Used as Tags to Mark the State of Protein Folding ER chaperone  THE ENDOPLASMIC RETICULUM Oligosaccharides Are Used as Tags to Mark the State of Protein Folding (213) – While still in the ER, two terminal glucoses (figure 47) are quickly removed from the oligosaccharides of most glycoproteins (con 1 glu) – Calnexin (ER chaperone) binds incompletely folded proteins via the signle terminal glucose and retains them in the ER until they are completely folded such that glycosyl transferase cannot bind them (figure 49). ↳ gas lai glu new fold sai -retry – Like cytosolic chaperones (chapter 6), -(calreticulin ER + chaperones prevent incompletely folded proteins calnexin) from aggregating within ER -  THE ENDOPLASMIC RETICULUM Misfolded Proteins in the ER Activate an Unfolded Protein Response – Cells carefully monitor the amount of misfolded protein in various compartments. – An accumulation of misfolded proteins in the cytosol, for example, triggers heat-shock response, which stimulates the transcription of genes encoding cytosolic chaperones that help to refold the proteins – Similarly, an accumulation of misfolded proteins in the ER triggers an unfolded protein response, which includes an increased transcription of genes (move) encoding ER chaperones and many other proteins that help to increase the protein-folding capacity of the ER – How do misfolded proteins in the ER signal to the nucleus for transcriptional activation? (figure 51) Misfolded Proteins in the ER Activate an Unfolded Protein Response Misfolded Proteins in the ER Activate an Unfolded Protein Response 3 Previous figure ways 3 sensors pass signal to nucleus y Inlui anh It protein prod deX misfolded Pre proteins) (XBP1) activeAne that makeperones