bumab Posted June 7, 2005 Author Report Posted June 7, 2005 True. But if we could demonstrate that a significant genetic change was actually pre-recognized by the parent species, imagine the implications. No kidding. How will you demonstrate that? :hyper:
Biochemist Posted June 7, 2005 Report Posted June 7, 2005 No kidding. How will you demonstrate that? :hyper:Good question. I am going to stew on this for a while.
bumab Posted June 7, 2005 Author Report Posted June 7, 2005 A thought- Insertion of new genes has not been a problem in many species. Genetic engineering does so all the time, and not just with plants. This is essentially a novel gene, and yet is not rejected out of hand. Even in the few human engineering projects, the rejection occured outside of cells, not on the inside (the cells were attacked from the outside). So, new genes do not apparently have to be recognized to persist (unless you say that since we're all decended from that first info prokaryote, we all recognize all other genes, but that's a stretch).
Biochemist Posted June 7, 2005 Report Posted June 7, 2005 ...Insertion of new genes has not been a problem in many species. Genetic engineering does so all the time, and not just with plants....So, new genes do not apparently have to be recognized to persist (unless you say that since we're all decended from that first info prokaryote, we all recognize all other genes, but that's a stretch).This is truly an interesting phenomenon. I was perusing the web on the recognition characteristics of lysosomes. Wouldn't it be odd if "live" genes were recognized, but "bogus" genes were not?
bumab Posted June 9, 2005 Author Report Posted June 9, 2005 A brief search on Google (and a trip to my old textbooks) brought an interesting point. There are basically two pathways protiens can travel to degredation. One is phagocytosis, where they get taken in from the outside in a vacoule which is degraded enzymatically really quick. That's not hard to understand, and besides the point to this discussion. The other is internal. The protiens to be degraded get tagged by ubiquitin and are degraded through protease activity. Apparently, ubliquitin is one of the most conserved protiens known, meaning the basic structure of ubiquitin has not changed over the years, and apparently significantly less overall then most other protiens. Facinating! I'm not sure whose hypothesis this applies most too, but if one were looking for a way to set up a functional protien mechanism, one would need a selection mechanism (ubiquitin) that wouldn't change along with the rest. http://www.neuro.wustl.edu/neuromuscular/mother/degrade.htm#ubiquitin That whole page has got a lot of good info.
Biochemist Posted June 9, 2005 Report Posted June 9, 2005 ...I'm not sure whose hypothesis this applies most too, but if one were looking for a way to set up a functional protien mechanism, one would need a selection mechanism (ubiquitin) that wouldn't change along with the rest....All good points, Bumab. Technically, I think lysosome action counts as phagocytosis too, since it grabs the ubiquitin tail and sucks the target protein into the lysosome lumen (where the pH is lower and there are lots of proteases). The issue is still how the phagocyte or lysosome recognizes the target protein. It is true that ubiquitin is tagged onto targets, but we still do not know how the cytosol machinery selects some proteins for destruction. We do know that once it decided, the target gets tagged with a couple of ubiquitin residues, and then the lysosomes routes it for destruction. But how does it decide which ones get broken down? I am still arguing that the DNA specifies it.
bumab Posted June 9, 2005 Author Report Posted June 9, 2005 But how does it decide which ones get broken down? I am still arguing that the DNA specifies it. Something must. It's hard to believe that the tagging protiens sequence somehow "knows" what to tag. Those protiens are not waving flags saying "I'm new here" so somebody has to know what's going on. Hmmm.... I was typing really fast and running out when I posted that, thanks for the correction.
TeleMad Posted June 10, 2005 Report Posted June 10, 2005 Technically, I think lysosome action counts as phagocytosis too... Not that I'm aware of. Phagocytosis ("cellular eating") involves taking bulk matter into the cells across the cell's plasma membrane. A lysosome is an organelle, not a cell. Biochemist: We do know that once it decided, the target gets tagged with a couple of ubiquitin residues, and then the lysosomes routes it for destruction. I believe you are wrong on your statments that it is the lysosomes that are responsible for degrading ubiquitin-tagged proteins. Off the top of my head, I believe it is something called a proteosome that is primarily responsible for that function.
TeleMad Posted June 10, 2005 Report Posted June 10, 2005 TeleMad: I believe you are wrong on your statments that it is the lysosomes that are responsible for degrading ubiquitin-tagged proteins. Off the top of my head, I believe it is something called a proteosome that is primarily responsible for that function. Couldn't resist looking it up. I was correct in saying that you were wrong when you said that lysosomes are responsible for degrading ubiquitin-tagged proteins, and I was already correct in stating what was responsible (but I mispelled the term proteosome; it's actually proteasome). "One major intracellular pathway [of protein degradation] involves degradation by enzymes within lysosomes, membrane-limited organelles whose interior is acidic. Distinct from the lysosomal pathway are cytosolic mechanisms for degrading proteins. The best-understood pathway, the ubiquitin-mediated pathways, involves two steps: addition of a chain of ubiquitin molecules to an internal lysine side chain of the target protein and proteolysis of the ubiquinated protein by a proteasome, a large, cylindrical multisubunit complex." (Molecular Cell Biology: Fourth Edition, Lodish, Berk, Zipursky, Matsudaira, Baltimore, & Darnell, W. H. Freeman & Co., 2000, p66-67)
Biochemist Posted June 10, 2005 Report Posted June 10, 2005 I was correct in saying that you were wrong when you said that lysosomes are responsible for degrading ubiquitin-tagged proteins, and I was already correct in stating what was responsible (but I mispelled the term proteosome; it's actually proteasome).That was thought to be true once. 1) "lysoome" is used ambiguously to mean either a set of degradatory intrecellular organelles, or a particular one.2) Recent discoveries have espanded the use of ubiquitin tagging to go beyond the proteasomes. See:http://www.news-medical.net/?id=5425 and dozens of other examples. Textbooks (even new ones) are at least 5 years out of date, sometimes ten.
Biochemist Posted June 10, 2005 Report Posted June 10, 2005 Not that I'm aware of. Phagocytosis ("cellular eating") involves taking bulk matter into the cells across the cell's plasma membrane. A lysosome is an organelle, not a cell.... Although most commonly cited examples of phagocytosis are indeed cellular and include the notion of production of phagosomes, the term is not restricited to external cell membranes. Induction of any substrate into to lumen of an organized system (organelle or not) is commonly referred to as phagocytosis as well. Note this reference from Wikipedia about subcategories of phagocytosis and the lysosome: http://en.wikipedia.org/wiki/Autophagy
bumab Posted June 10, 2005 Author Report Posted June 10, 2005 Do you know the recognition criteria for ubiquitin? Since ubiquitin is so well conserved, presumably the recognition criteria have remained unchanged. I almost think that supports your theory, Bio.
Biochemist Posted June 10, 2005 Report Posted June 10, 2005 Do you know the recognition criteria for ubiquitin? Since ubiquitin is so well conserved, presumably the recognition criteria have remained unchanged. I almost think that supports your theory, Bio.This is a really interesting area. I think ubiquitin was only discovered in the '80s (anyone?) and it was initially described in relation to tagging for protein degradation. More recent studies have confirmed the role of protein transport (e.g., from the nucleus to the cytosol) in advance of proteolysis. But recent studies suggest that the ubiquitin tagging function controls a myriad of intracellular functions by routing proteins for degradation. There are also some suggestions that ubiquitin flags some proteins for transport to locations other than degradation sites. See: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=14570567&dopt=Abstract I still don't think we know how ubiquitin identifies its targets. This is a pretty intriging function. If we can confirm that any viable protein also needs to have a viable destruction control mechanism, it would put one more nail in the coffin of mutation based speciation.
TeleMad Posted June 10, 2005 Report Posted June 10, 2005 TeleMad: Not that I'm aware of. Phagocytosis ("cellular eating") involves taking bulk matter into the cells across the cell's plasma membrane. A lysosome is an organelle, not a cell. Biochemist: Although most commonly cited examples of phagocytosis are indeed cellular and include the notion of production of phagosomes, the term is not restricited to external cell membranes. Induction of any substrate into to lumen of an organized system (organelle or not) is commonly referred to as phagocytosis as well. And your support for that claim? Absent. Biochemist: Note this reference from Wikipedia about subcategories of phagocytosis and the lysosome: http://en.wikipedia.org/wiki/Autophagy 1) That page discusses AUTOphagy, NOT phagocytosis. In fact, the term phagocytosis doesn't even appear on that page you link to in order to supposely support your position. 2) The Wikipedia page for phagocytosis doesn't include the term AUTOphagy on it anywhere. You have provided no evidence to support your assertion.
bumab Posted June 10, 2005 Author Report Posted June 10, 2005 Doesn't really matter, since we were discussing ubiquitation, which is an entirely different pathway.
TeleMad Posted June 10, 2005 Report Posted June 10, 2005 To support my usage of the term phagocytosis, I’ll present 2 or 3 quotes from several college biology texts: all emphasis (bold and italics) are in the original books. First text… “phagocytosis Process by which relatively large particles (e.g., bacterial cells) are internalized by certain eukaryotic cells.” (Molecular Cell Biology: Fourth Edition, Lodish, Berk, Zipursky, Matsudaira, Baltimore, & Darnell, W. H. Freeman & Co., 2000, pG-13) “Endocytosis refers to the process by which extracellular materials are taken up by invagination of a segment of the plasma membrane to form a small membrane-bounded vesicle (endosome). In phagocytosis, relatively large particles are enveloped by the plasma membrane and internalized.” (Molecular Cell Biology: Fourth Edition, Lodish, Berk, Zipursky, Matsudaira, Baltimore, & Darnell, W. H. Freeman & Co., 2000, p169) “In previous sections, we’ve followed the main pathways whereby secretory and membrane proteins are synthesized within cells and then targeted to the cell surface or other destination. However, cells also can internalize materials from their surroundings by phagocytosis, an actin-mediated process in which cells envelop bacteria and other large particles and then internalize them.” (Molecular Cell Biology: Fourth Edition, Lodish, Berk, Zipursky, Matsudaira, Baltimore, & Darnell, W. H. Freeman & Co., 2000, p727) Second text… phagocytosis: The engulfing of extracellular materials or pathogens; the movement of extracellular materials into the cytoplasm by enclosure in a membranous vesicle.” (Fundamentals of Anatomy & Physiology: Sixth Edition, Frederic H. Martinin, Benjamin Cummings, 2004, pG-20) Phagocytosis: Cell eating, or phagocytosis, produces phagosomes containing solid objects that may be as large as the cell itself.” (Fundamentals of Anatomy & Physiology: Sixth Edition, Frederic H. Martinin, Benjamin Cummings, 2004, p98) Third text… ”Some protozoa, for example, take up food particles or other materials from their environment by a process called phagocytosis (“cell eating”). Phagocytosis is a form of endocytosis that involves an inpocketing of the plasma membrane around the desired substance, followed by a pinching-off process that internalizes the membrane-bounded particle as a vacuole.” (The World of the Cell: Third Edition, Becker, Reece, & Poenie, Benjamin Cummings, 1996, p98-99) ”In addition, some cells can take up much larger particles, including whole cells, by phagocytosis, a process seen most prominently among single-celled heterotrophs. These organisms routinely engulf and internalize food particles and smaller organisms for intracellular digestion. Phagocytosis is also used by some primitive animals, notably flatworms, coelenterates, and sponges, as a means of obtaining nutrients. In higher organisms, phagocytosis is usually restricted to specialized cells called phagocytes. Your body, for example, contains two classes of white blood cells that function as phagocytes: macrophages and neutrophils (also called polymorphonuclear leukocytes).” (The World of the Cell: Third Edition, Becker, Reece, & Poenie, Benjamin Cummings, 1996, p256) Fourth text… ”phagocytosis The engulfment of a particle by a phagocyte or protozoan.” (Integrated Principles of Zoology: Tenth Edition, Hickman, Roberts, and Larson, McGraw Hill, 1996, p861) ”Phagocytosis, which literally means “cell eating”, is a common method of feeding among protozoa and lower metazoan. It is also the way in which white blood cells (leukocytes) engulf cellular debris and uninvited microbes in the blood. By phagocytosis, an area of the cell membrane, coated internally with actin-myosin, forms a pocket that engulfs the solid material. The membrane-enclosed vesicle then detaches from the cell surface and moves into the cytoplasm where its contents are digested by intracellular enzymes.” (Integrated Principles of Zoology: Tenth Edition, Hickman, Roberts, and Larson, McGraw Hill, 1996, p53-54) Fifth text… phagocytosis Literally, “cell eating”; a type of endocytosis by which certain cells engulf food particles, microorganisms, foreign matter, or other cells.” (Biology: Fifth Edition, Solomon, Berg, & Martin, Harcourt College Publishing, 1999, pG-30) ”Several types of endocytotic mechanisms operate in biological systems including phagocytosis, pinocytosis, and receptor-mediated endocytosis. In phagocytosis (literally, “cell eating”), the cell ingests solid particles such as bacteria or food. Phagocytosis is a mechanism used by certain protests and be several types of vertebrate white blood cells to ingest particles, some of which are a large as an entire bacterium. During ingestion, folds of the plasma membrane enclose the particle, which has bound to the surface of the cell, forming a large membranous sac, or vacuole. When the membrane has encircled the particle, it fuses at the point of contact.” (Biology: Fifth Edition, Solomon, Berg, & Martin, Harcourt College Publishing, 1999, p123) And of course, in addition to these quotes that show Biochemist's usage to be wrong, there is also the Wikipedia page on phagocytosis... ”Phagocytosis (literally, "cell eating") is a form of endocytosis where large particles are enveloped by the cell membrane of a (usually larger) cell and internalized to form a phagosome, or "food vacuole." In animals, phagocytosis is performed by specialized cells called phagocytes, which serve to remove foreign bodies and thus fight infection. In vertebrates these include larger macrophages and smaller granulocytes, types of blood cells. Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed. Virulent bacteria may need to be coated in antibodies before it is possible to consume them. Certain pathogenic bacteria, such as those of leprosy and tuberculosis, are resistant to phagocytosis. In many protists, phagocytosis is used as a means of feeding, providing part or all of their nourishment. This is called phagotrophic nutrition, as distinguished from osmotrophic nutrition which takes place by absorption. In some, such as amoebae, phagocytosis takes place by surrounding the target object with pseudopods, as in animal phagocytes. In other protozoa, for instance ciliates, there is a specialized groove or chamber in the cell where phagocytosis takes place, called the cytostome or mouth. The resulting phagosome may be merged with lysosomes containing digestive enzymes, and the resulting material is absorbed into the cytosol.” (http://en.wikipedia.org/wiki/Phagocytosis) See, no mention of autophagy anywhere in there. And, the definition itself and all examples involve CELLs internalizing bulk materials.
bumab Posted June 10, 2005 Author Report Posted June 10, 2005 Again, TM, who cares? How does the specific definition of phagocytosis apply to the discussion? We were discussing how new protiens from genetic mutations escape being destroyed through the self-protective mechanisms of cells.
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