Eukaryotic Cell Organelles & Protein Trafficking PDF

the nucleolus is not enclosed by a membrane and represents one example of a biomolecular condensate. In liver and pancreatic cells, for example, the endoplasmic reticulum has a total membrane surface area that is, respectively, 25 times and 12 times that of the plasma membrane. The membrane-encl...

the nucleolus is not enclosed by a membrane and represents one example of a biomolecular condensate. In liver and pancreatic cells, for example, the endoplasmic reticulum has a total membrane surface area that is, respectively, 25 times and 12 times that of the plasma membrane. The membrane-enclosed organelles are packed tightly in the cytoplasm, and, in terms of area and mass, the plasma membrane is only a minor membrane in most eukaryotic cells There is evidence that the first eukaryotic cells arose when an ancient anaerobic archaeon joined forces with an aerobic bacterium roughly 1.6 billion years ago. An early step in this process was ˘v]}v}(ZZ}v[ouuuv , probably through protrusions and blebs. The highly curved membrane at the necks of these protrusions might have been stabilized by proteins that eventually became part of the nuclear pore. The added surface area of these protrusions facilitated metabolite exchange with the environment and with neighboring cells. A fruitful symbiotic relationship with an aerobic bacterium might have allowed the archaeon to increase in volume. These protrusions eventually fused with each other to pinch off internal membrane-enclosed compartments, some of which contained the symbiotic bacteria. This intermediate now begins to resemble modern-day eukaryotes, with a primordial nucleus and nuclear pores, internal compartments, and an endosymbiont destined to become the mitochondrion. The lumen of the internal compartments is topologically equivalent to the extracellular space. The membrane- enclosed endosymbiont subsequently escaped the enclosing membrane into the cytosol where it evolved into modern-day mitochondria. The internal compartments expanded and became progressively specialized to form the major intracellular compartments of a eukaryotic cell. Their common origin from a primordial intracellular compartment explains why all of these compartments can exchange material with each other through vesicular transport. The nucleus was formerly the cytosol in the ancient archaeon, explaining why the cytosol and nucleus are topologically equivalent compartments that can intermix during mitosis.  plasma m e m b r a n e rough R E lysosome cargo molecule nucle us compartment 1 transport vesicle compartment 2 inner nuclear membrane outer nuclear membrane apparatus secretory vesicle nuclear envelope endosome (A) (B) Topologically equivalent compartments in the secretory and endocytic pathways in a eukaryotic cell. Topologically equivalent spaces are shown in red. (A) Molecules can be carried from one compartment to another topologically equivalent compartment by transport vesicles that bud from one and fuse with the other. (B) In principle, cycles of membrane budding and fusion permit the lumen of any of the organelles shown o t communicate with any other and with the cell exterior by means of transport vesicles. Blue arrows indicate the extensive outbound and inbound vesicular traffic Some organelles, most notably mitochondria and (in plant cells) plastids, do not take part in this communication and are isolated from the vesicular traffic between organelles shown here. NUCLEOLUS An electron micrograph of the rough ER in a pancreatic exocrine cell that makes and secretes large amounts of digestive enzymes every day. The cytosol is filled with closely packed sheets of ER membrane that are studded with ribosomes. Abundant smooth ER in a cell that secretes steroid hormone. This electron micrograph is of a testosterone-secreting Leydig cell in the human testis. The Endoplasmic Reticulum (ER) Ca2+ Store and ER Mitochondria Contact Sites To study the functions and biochemistry of the ER, it is necessary to isolate it. This may seem to be a hopeless task because the ER is intricately interleaved with other components of the cytoplasm. Fortunately, when tissues or cells are disrupted by homogenization, the ER breaks into fragments, which reseal to form small ( 100 200 nm in diameter) closed vesicles called microsomes. To the biochemist, microsomes represent small authentic versions of the ER, still capable of protein translocation, protein glycosylation, Ca2+ uptake and release, and lipid synthesis. Rough microsomes, derived from rough ER, contain ribosomes on their outside surface and enclose a small part of the ER lumen. Smooth microsomes, which lack ribosomes, are derived from vesiculated fragments of the smooth ER, plasma membrane, Golgi apparatus, endosomes, and mitochondria. The ribosomes attached to rough microsomes make them denser than smooth microsomes. As a result, scientists use equilibrium density centrifugation to separate the rough and smooth Membrane-bound ribosomes, attached to the cytosolic side of the ER membrane, are engaged in the synthesis of proteins that are being concurrently translocated across the ER membrane. Free ribosomes, unattached to any membrane, synthesize all other proteins encoded by the nuclear genome. Membrane-bound and free ribosomes are structurally and functionally identical. They differ only in the proteins they are making at any given time. Because many ribosomes can engage with a single mRNA molecule, a polyribosome is usually formed. If the mRNA encodes a protein with an ER signal sequence, the polyribosome becomes attached to the ER membrane, directed there by the signal sequences on multiple growing polypeptide chains. Sec61 translocator  I THE ER MEMBRANE, PHOSPHOLIPIDS N IN THE GOLGI AND OTHER CELL MEMBRANES, ARE RANDOMLY DISTRIBUTED PHOSPHOLIPID DISTRIBUTION S I ASYMMETRIC CYTOSOL GOLGI LUMEN Because phospholipid synthesis takes place in the cytosolic leaflet of 0000000000006680001 the ER lipid bilayer, there needs to be a mechanism that transfers some of the newly formed phospholipid molecules to the lumenal leaflet of the 00000 bilayer. ER LUMEN CYTOSOL Golgi membrane In the ER, phospholipids equilibrate across the membrane within minutes, which is almost 100,000 times faster than can PHOSPHOLIPID SYNTHESIS DELIVERY OF ADDS TO CYTOSOLIC HALF NEW MEMBRANE be accounted for by spontaneous "flip-flop." This rapid trans-bilayer OF THE BILAYER FROM ER asymmetric movement si mediated by a poorly characterized phospholipid translocator growth of scramblase flippase bilayer called a scramblase, which nonselectively equilibrates phospholipids between the two leaflets of the lipid bilayer. Thus, the different types of phospholipids are thought to be equally distributed between the two leaflets of the ER membrane. SCRAMBLASES CATALYZE FLIPPASES CATALYZE TRANSFER O F RANDOM TRANSFER OF SPECIFIC PHOSPHOLIPIDS FROM ONE PHOSPHOLIPIDS TO THE MONOLAYER TO ANOTHER OPPOSITE MONOLAYER symmetric growth of bilayer growth of asymmetric bilayer