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Cell–cell recognition

From Wikipedia, the free encyclopedia

Two cells communicating via their respective surface molecules.
Two cells communicating via their respective surface molecules.

Cell–cell recognition is a cell's ability to distinguish one type of neighboring cell from another.[1] This phenomenon occurs when complementary molecules on opposing cell surfaces meet. A receptor on one cell surface binds to its specific ligand on a nearby cell, initiating a cascade of events which regulate cell behaviors ranging from simple adhesion to complex cellular differentiation.[2] Like other cellular functions, cell-cell recognition is impacted by detrimental mutations in the genes and proteins involved and is subject to error. The biological events that unfold due to cell-cell recognition are important for animal development, microbiomes, and human medicine.

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Transcription

This is an animal. This is also an animal. Animal. Animal. Animal carcass. Animal. Animal. Animal carcass again. Animal. The thing that all of these other things have in common is that they're made out of the same basic building block: the animal cell. Animals are made up of your run-of-the-mill eukaryotic cells. These are called eukaryotic because they have a "true kernel," in the Greek. A "good nucleus". And that contains the DNA and calls the shots for the rest of the cell also containing a bunch of organelles. A bunch of different kinds of organelles and they all have very specific functions. And all this is surrounded by the cell membrane. Of course, plants have eukaryotic cells too, but theirs are set up a little bit differently, of course they have organelles that allow them to make their own food which is super nice.  We don't have those. And also their cell membrane is actually a cell wall that's made of cellulose. It's rigid, which is why plants can't dance. If you want to know all about plant cells, we did a whole video on it and you can click on it here if it's online yet. It might not be. Though a lot of the stuff in this video is going to apply to all eukaryotic cells, which includes plants, fungi and protists.   Now, rigid cells walls are cool and all, but one of the reasons animals have been so successful is that their flexible membrane, in addition to allowing them the ability to dance, gives animals the flexibility to create a bunch of different cell types and organs types and tissue types that could never be possible in a plant. The cell walls that protect plants and give them structure prevent them from evolving complicated nerve structures and muscle cells, that allow animals to be such a powerful force for eating plants. Animals can move around, find shelter and food, find things to mate with all that good stuff.  In fact, the ability to move oneself around using specialized muscle tissue has been 100% trademarked by kingdom Animalia. >>OFF CAMERA: Ah! What about protozoans? Excellent point! What about protozoans? They don't have specialized muscle tissue.  They move around with cillia and flagella and that kind of thing. So, way back in 1665, British scientist Robert Hooke discovered cells with his kinda crude, beta version microscope. He called them "cells" because hey looked like bare, spartan monks' bedrooms with not much going on inside. Hooke was a smart guy and everything, but he could not have been more wrong about what was going on inside of a cell.  There is a whole lot going on inside of a eukaryotic cell. It's more like a city than a monk's cell.  In fact, let's go with that a cell is like a city. It has defined geographical limits, a ruling government, power plants, roads, waste treatment plants, a police force, industry...all the things a booming metropolis needs to run smoothly.  But this city does not have one of those hippie governments where everybody votes on stuff and talks things out at town hall meetings and crap like that.  Nope.  Think fascist Italy circa 1938.  Think Kim Jong Il's- I mean, think Kim Jong-Un's North Korea, and you might be getting a closer idea of how eukaryotic cells do their business.   Let's start out with city limits. So, as you approach the city of Eukaryopolis there's a chance that you will notice something that a traditional city never has, which is either cilia or flagella.  Some eukaryotic cells have either one or the other of these structures--cilia being a bunch of little tiny arms that wiggle around and flagella being one long whip-like tail.  Some cells have neither. Sperm cells, for instance, have flagella, and our lungs and throat cells have cilia that push mucus up and out of our lungs.  Cilia and flagella are made of long protein fibers called microtubules, and they both have the same basic structure: 9 pairs of microtubules forming a ring around 2 central microtubules. This is often called the 9+2 structure. Anyway, just so you know--when you're approaching city, watch out for the cilia and flagella! If you make it past the cilia, you'll encounter what's called a cell membrane, which is kind of squishy, not rigid, plant cell wall, which totally encloses the city and all its contents.  It's also in charge of monitoring what comes in and out of the cell--kinda like the fascist border police. The cell membrane has selective permeability, meaning that it can choose what molecules come in and out of the cells, for the most part.   And I did an entire video on this, which you can check out right here. Now the landscape of Eukaryopolis, it's important to note, is kind of wet and squishy. It's a bit of a swampland. Each eukaryotic cell is filled with a solution of water and nutrients called cytoplasm.  And inside this cytoplasm is a sort of scaffolding called the cytoskeleton, it's basically just a bunch of protein strands that reinforce the cell.  Centrosomes are a special part of this reinforcement; they assemble long microtubules out of proteins that act like steel girders that hold all the city's buildings together. The cytoplasm provides the infrastructure necessary for all the organelles to do all of their awesome, amazing business, with the notable exception of the nucleus, which has its own special cytoplasm called "nucleoplasm" which is a more luxurious, premium environment befitting the cell's Beloved Leader. But we'll get to that in a minute.   First, let's talk about the cell's highway system, the endoplasmic reticulum, or just ER, are organelles that create a network of membranes that carry stuff around the cell. These membranes are phospholipid bilayers. The same as in the cell membrane. There are two types of ER: there's the rough and the smooth. They are fairly similar, but slightly different shapes and slightly different functions. The rough ER looks bumpy because it has ribosomes attached to it, and the smooth ER doesn't, so it's a smooth network of tubes. Smooth ER acts as a kind of factory-warehouse in the cell city. It contains enzymes that help with the creation of important lipids, which you'll recall from our talk about biological molecules -- i.e. phosopholipids and steroids that turn out to be sex hormones. Other enzymes in the smooth ER specialize in detoxifying substances, like the noxious stuff derived from drugs and alcohol, which they do by adding a carboxyl group to them, making them soluble in water. Finally, the smooth ER also stores ions in solutions that the cell may need later on, especially sodium ions, which are used for energy in muscle cells.   So the smooth ER helps make lipids, while the rough ER helps in the synthesis and packaging of proteins. And the proteins are created by another typer of organelle called the ribosome. Ribosomes can float freely throughout the cytoplasm or be attached to the nuclear envelope, which is where they're spat out from, and their job is to assemble amino acids into polypeptides. As the ribosome builds an amino acid chain, the chain is pushed into the ER. When the protein chain is complete, the ER pinches it off and sends it to the Golgi apparatus. In the city that is a cell, the Golgi is the post office, processing proteins and packaging them up before sending them wherever they need to go. Calling it an apparatus makes it sound like a bit of complicated machinery, which it kind of is, because it's made up of these stacks of membranous layers that are sometimes called Golgi bodies. The Golgi bodies can cut up large proteins into smaller hormones and can combine proteins with carbohydrates to make various molecules, like, for instance, snot.   The bodies package these little goodies into sacs called vesicles, which have phosopholipid walls just like the main cell membrane, then ships them out, either to other parts of the cell or outside the cell wall. We learn more about how vesicles do this in the next episode of Crash Course. The Golgi bodies also put the finishing touches on the lysosomes. Lysosomes are basically the waste treatment plants and recycling centers of the city. These organelles are basically sacks full of enzymes that break down cellular waste and debris from outside of the cell and turn it into simple compounds, which are transferred into the cytoplasm as new cell-building materials. Now, finally, let us talk about the nucleus, the Beloved Leader.  The nucleus is a highly specialized organelle that lives in its own double-membraned, high-security compound with its buddy the nucleolus.  And within the cell, the nucleus is in charge in a major way.  Because it stores the cell's DNA, it has all the information the cell needs to do its job. So the nucleus makes the laws for the city and orders the other organelles around, telling them how and when to grow, what to metabolize, what proteins to synthesize, how and when to divide. The nucleus does all this by using the information blueprinted in its DNA to build proteins that will facilitate a specific job getting done.  For instance, on January 1st, 2012, lets say a liver cell needs to help break down an entire bottle of champagne. The nucleus in that liver cell would start telling the cell to make alcohol dehydrogenase, which is the enzyme that makes alcohol not-alcohol anymore. This protein synthesis business is complicated, so lucky for you, we will have or may already have an entire video about how it happens. The nucleus holds its precious DNA, along with some proteins, in a weblike substance called chromatin. When it comes time for the cell to split, the chromatin gathers into rod-shaped chromosomes, each of which holds DNA molecules. Different species of animals have different numbers of chromosomes. We humans have 46. Fruit flies have 8. Hedgehogs, which are adorable, are less complex than humans and have 90 Now the nucleolus, which lives inside the nucleus, is the only organelle that's not enveloped by its own membrane--it's just a gooey splotch of stuff within the nucleus. Its main job is creating ribosomal RNA, or rRNA, which it then combines with some proteins to form the basic units of ribosomes. Once these units are done, the nucleolus spits them out of the nuclear envelope, where they are fully assembled into ribosomes. The nucleus then sends orders in the form of messenger RNA, or mRNA, to those ribosomes, which are the henchmen that carry out the orders in the rest of the cell. How exactly the ribosomes do this is immensely complex and awesome, so awesome, in fact, that we're going to give it the full Crash Course treatment in an entire episode. And now for what is, totally objectively speaking of course, the coolest part of an animal cell: its power plants!  The mitochondria are these smooth, oblong organelles where the amazing and super-important process of respiration takes place. This is where energy is derived from carbohydrates, fats and other fuels and is converted into adenosine triphosphate or ATP, which is like the main currency that drives life in Eukaryopolis. You can learn more about ATP and respiration in an episode that we did on that. Now of course, some cells, like muscle cells or neuron cells need a lot more power than the average cell in the body, so those cells have a lot more mitochondria per cell.   But maybe the coolest thing about mitochondria is that long ago animal cells didn't have them, but they existed as their own sort of bacterial cell. One day, one of these things ended up inside of an animal cell, probably because the animal cell was trying to eat it, but instead of eating it, it realized that this thing was really super smart and good at turning food into energy and it just kept it. It stayed around. And to this day they sort of act like their own, separate organisms, like they do their own thing within the cell, they replicate themselves, and they even contain a small amount of DNA. What may be even more awesome -- if that's possible -- is that mitochondria are in the egg cell when an egg gets fertilized, and those mitochondria have DNA. But because mitochondria replicate themselves in a separate fashion, it doesn't get mixed with the DNA of the father, it's just the mother's mitochondrial DNA. That means that your and my mitochondrial DNA is exactly the same as the mitochondrial DNA of our mothers. And because this special DNA is isolated in this way, scientists can actually track back and back and back and back to a single "Mitochondrial Eve" who lived about 200,000 years ago in Africa.   All of that complication and mystery and beauty in one of the cells of your body. It's complicated, yes. But worth understanding. Review time! Another somewhat complicated episode of Crash Course Biology. If you want to go back and watch any of the stuff we talked about to reinforce it in your brain or if you didn't quite get it, just click on the links and it'll take you back in time to when I was talking about that mere minutes ago. Thank you for watching. If you have questions for us please ask below in the comments, or on Twitter, or on Facebook. And we will do our best to make things more clear for you. We'll see you next time.

Fundamentals

Cell–cell recognition occurs when two molecules restricted to the plasma membranes of different cells bind to each other, triggering a response for communication, cooperation, transport, defense, and/or growth. Rather than induce a distal response, like secreted hormones may do, this type of binding requires the cells with the signalling molecules to be in close proximity with each other. These events can be grouped into two main categories: Intrinsic Recognition and Extrinsic Recognition.[3] Intrinsic Recognition is when cells that are part of the same organism associate.[3] Extrinsic Recognition is when the cell of one organism recognizes a cell from another organism, like when a mammalian cell detects a microorganism in the body.[3] The molecules that complete this binding consist of proteins, carbohydrates, and lipids, resulting in a variety of glycoproteins, lipoproteins, and glycolipoproteins.[3] Studies suggest glycan-glycan interactions, observed to be approximately 200-300pN, also may play a role in cell-cell recognition.[4] Complex carbohydrates, in particular, have been studied to be extremely integral in cell-cell recognition, especially when it is recognized by complementary carbohydrates. In order to ensure a proper binding site by checking the surrounding areas or securing a bond that was previously made complex carbohydrates and their complementary carbohydrates are able to create flexible interaction systems. These interactions, although observed to be weak, have been studied in a variety of test subjects including, but not limited to, mouse embryonal cells, corneal epithelial cells, and human embryonal carcinoma cells.[4]

Biological functions for intrinsic recognition

Growth and development

One of the more basic versions of cell-cell recognition for adhesion can be observed in sponges, the most primitive group in the animal kingdom. Sponges develop through the aggregation of individual cells into larger clusters. Through membrane-binding proteins and secreted ions, individual sponge cells are able to coordinate aggregation while preventing fusion between different species or even different individuals.[5] This was discovered when attempts to graft sponge cells from different species or individuals of the same species failed, while attempts using cells from the same individual merged successfully.[5] This is likely due to distinct cadherins, a calcium-binding membrane protein, expressed by different sponge species and individuals.[5] Cadherins are present in more complex organisms as well. In mouse embryos, E-cadherin on cell membranes is responsible for the adhesion of cells needed for embryonic compaction.[6]

Cell recognition for injury response

When a large multi-cellular organism sustains an injury, cell-cell recognition is often involved in bringing certain types of cells to the site of an injury. A common example of this is selectin-expressing cells in animals. Selectin is a receptor protein found on the membranes of leukocytes, platelet cells, and endothelial cells that binds membrane-bound glycans.[7] In response to an injury, endothelial cells will express selectin, which binds to glycans present on the leukocyte cell surface.[7] Platelet cells, which are involved in tissue repair, use their selectins to associate with leukocytes on the way to the endothelial cells.[7] Leukocytes then use their own selectins to recognize potential pathogens at the site of the injury.[7] In this manner, the appropriate cells are brought to the site of an injury to deal with immediate repair or invading microorganisms.[7]

Biological functions for extrinsic recognition

Pathogen recognition in the immune system

Cells with immune system recognition abilities include macrophages, dentritic cells, T cells, and B cells.[8] Cell–cell recognition is especially important in the innate immune system, which identifies pathogens very generally. Central to this process is the binding of pattern recognition receptors (PRRs) of phagocytes and pathogen-associated molecular patterns (PAMPs) in pathogenic microorganisms.[8] One type of PRR is a group of integral membrane glycoproteins called toll-like receptors (TLRs), which can recognize certain lipoproteins, peptidoglycan, CpG-rich DNA, and flagellar components in bacterial cells, as well as glycoproteins and phospholipids from protozoan parasites and conidia (fungal spores).[8] The binding of PAMPs to TLR proteins generally results in an internal signaling cascade including a number of phosphorylations, the adding of a phosphate group, and ubiquitinations, the adding of a small protein that marks molecules for degradation, that eventually leads to the transcription of genes related to inflammation.[8] The use of TLRs by cells in the innate immune system has led to an evolutionary battle between pathogenic cells developing different PAMPs that cannot be recognized and immune cells developing new membrane proteins that can recognize them.[8]

Bacterial ecology

Single-celled organisms can bind to each other through surface receptors for cooperation and competition. This has been widely observed in bacteria. For instance, bacteria can attach to each other through the binding of outer membrane proteins TraA and TraB to facilitate a process called outer membrane exchange (OME) that allows bacterial cells to swap membrane lipids, sugars, and toxins.[9] Cell recognition and OME can only be achieved if TraA and TraB variants from the same recognition group bind.[9] These interactions can generate the physiological diversity required for antibiotic resistance in bacterial populations.[10] The Escherichia coli membrane protein ChiA is involved in the process of contact-dependent inhibition (CDI) in which it binds to receptors on rival E.coli strains and releases a toxin that prevents growth of those strains while the inhibiting cell and members of that strain are protected.[9] The bacterium Proteus mirabilis uses the T6SS protein to initiate swarming and destruction of other bacterial colonies upon recognition, either by release of toxins or by release of signal proteins to other P. mirabilis cells.[9] The binding of bacterial surface receptors for adhesion has also been implicated in the formation of biofilms.[9]

Recognition of red blood cells

Blood types

Red blood cells contain antigens in their plasma membranes that distinguish them as part of a specific category of blood cell. These antigens can be polysaccharides, glycoproteins, or GPI (a glycolipid) -linked proteins.[11] Antigens range in complexity, from small molecules bound to the extracellular side of the phospholipid bilayer, to large membrane proteins that loop many times between both sides of the membrane.[11] The smaller polysaccharide antigens classify blood cells into types A, B, AB, and O, while the larger protein antigens classify blood cells into types Rh D-positive and Rh D-negative.[11] While the biological role of the correct blood type is unclear and may be vestigial, the consequences of incorrect blood types are known to be severe.[11] The same cells that recognize PAMPs on microbial pathogens may bind to the antigen of a foreign blood cell and recognize it as a pathogen because the antigen is unfamiliar.[11] It is not easy to classify red blood cell recognition as intrinsic or extrinsic, as a foreign cell may be recognized as part of the organism if it has the right antigens.

Detrimental mutations

TLR mutations

Mutations in mammalian receptor proteins can cause disorders in cell-cell recognition, increasing individual susceptibility to certain pathogens and chronic conditions. When mutations occurs in genes that code for TLRs, the proteins can lose the ability to bind with polysaccharides, lipids, or proteins on the cell wall or membrane of single-celled pathogens, resulting in a failure of the innate immune system to respond to infection that allows disease to develop rapidly. In particular, mutations in the genes for TLR2 and TLR4 have been frequently implicated in increased susceptibility to pathogens.[12] A threonine to cysteine mutation in the TRL2 gene has been connected to failure to recognize the Mycobacterium tuberculosis the causative agent of Tuberculosis meningitis.[13] The same mutation, T597C, was later observed consistently with the failure to recognize Mycobacterium leprae, the causative agent of Leprosy.[14] An Arginine to Glutamine mutation in TRL2, Arg753Gln, was connected to increased pediatric Urinary Tract Infections caused by gram-positive bacteria.[15] Multiple mutations in TLR4, Asp299Gly and Thr399Ile, were implicated in susceptibility to the bacterial pathogens that cause Periodontitis.[16] The connection of TLR mutations to Chron's Disease has also been investigated, but has not yielded conclusive evidence.[17] The common characteristic between these missense mutations is that the amino acid residues that are substituted have notably different side chain properties, which likely contributes to the defective TLR protein function.

References

  1. ^ Campbell, et al., Biology, Eighth Edition, 2008 Pearson Education Inc.
  2. ^ Schnaar, Ronald L., Research Goals, "Link", 1 May 2010
  3. ^ a b c d Ajit Varki and John B Lowe, Biological Roles of Glycans, Essentials of Glycobiology, 2nd Edition Cold Spring Harbor, 2009[page needed]
  4. ^ a b Bucior, Iwona; Burger, Max M (October 2004). "Carbohydrate–carbohydrate interactions in cell recognition". Current Opinion in Structural Biology. 14 (5): 631–637. doi:10.1016/j.sbi.2004.08.006. PMID 15465325.
  5. ^ a b c Fernàndez-Busquets, Xavier; Burger, Max M. (1999). "Cell adhesion and histocompatibility in sponges". Microscopy Research and Technique. 44 (4): 204–218. doi:10.1002/(SICI)1097-0029(19990215)44:4<204::AID-JEMT2>3.0.CO;2-I. PMID 10098923. S2CID 36978646.
  6. ^ Li, Chao-Bo; Hu, Li-Li; Wang, Zhen-Dong; Zhong, Shu-Qi; Lei, Lei (22 December 2009). "Regulation of compaction initiation in mouse embryo: Regulation of compaction initiation in mouse embryo". Yi Chuan = Hereditas. 31 (12): 1177–1184. doi:10.3724/sp.j.1005.2009.01177. PMID 20042384.
  7. ^ a b c d e Richard D Cummings and Rodger P McEver, C-type lectins, Essentials of Glycobiology, 2nd Edition Cold Spring Harbor, 2009[page needed]
  8. ^ a b c d e Akira, Shizuo; Uematsu, Satoshi; Takeuchi, Osamu (February 2006). "Pathogen Recognition and Innate Immunity". Cell. 124 (4): 783–801. doi:10.1016/j.cell.2006.02.015. PMID 16497588. S2CID 14357403.
  9. ^ a b c d e Troselj, Vera; Cao, Pengbo; Wall, Daniel (March 2018). "Cell-cell recognition and social networking in bacteria: Cell recognition and social networking". Environmental Microbiology. 20 (3): 923–933. doi:10.1111/1462-2920.14005. PMC 5874169. PMID 29194914.
  10. ^ Christopher N Vassallo, P Cao, A Conklin, H Finkelstein, CS Hayes, D Wall. Infectious polymorphic toxins delivered by outer membrane exchange discriminate kin in myxobacteria. 2017. eLife Microbiology and Infectious Disease[page needed]
  11. ^ a b c d e Laura Dean. Blood group antigens are surface markers on the red blood cell membrane. Blood Groups and Red Cell Antigens. 2005. National Center for Biotechnology Information[page needed]
  12. ^ Bhide, Mangesh R; Mucha, Rastislav; Mikula, Ivan; Kisova, Lucia; Skrabana, Rostislav; Novak, Michal; Mikula, Ivan (December 2009). "Novel mutations in TLR genes cause hyporesponsiveness to Mycobacterium avium subsp. paratuberculosis infection". BMC Genetics. 10 (1): 21. doi:10.1186/1471-2156-10-21. PMC 2705378. PMID 19470169.
  13. ^ Thuong, N. T. T.; Hawn, T. R.; Thwaites, G. E.; Chau, T. T. H.; Lan, N. T. N.; Quy, H. T.; Hieu, N. T.; Aderem, A.; Hien, T. T.; Farrar, J. J.; Dunstan, S. J. (July 2007). "A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis". Genes & Immunity. 8 (5): 422–428. doi:10.1038/sj.gene.6364405. PMID 17554342. S2CID 24528072.
  14. ^ Bochud, Pierre‐Yves; Hawn, Thomas R.; Siddiqui, M. Ruby; Saunderson, Paul; Britton, Sven; Abraham, Isaac; Argaw, Azeb Tadesse; Janer, Marta; Zhao, Lue Ping; Kaplan, Gilla; Aderem, Alan (15 January 2008). "Toll‐Like Receptor 2 (TLR2) Polymorphisms Are Associated with Reversal Reaction in Leprosy". The Journal of Infectious Diseases. 197 (2): 253–261. doi:10.1086/524688. PMC 3077295. PMID 18177245.
  15. ^ Tabel, Y.; Berdeli, A.; Mir, S. (December 2007). "Association of TLR2 gene Arg753Gln polymorphism with urinary tract infection in children". International Journal of Immunogenetics. 34 (6): 399–405. doi:10.1111/j.1744-313X.2007.00709.x. PMID 18001294. S2CID 35652649.
  16. ^ Fukusaki, T.; Ohara, N.; Hara, Y.; Yoshimura, A.; Yoshiura, K. (December 2007). "Evidence for association between a Toll-like receptor 4 gene polymorphism and moderate/severe periodontitis in the Japanese population". Journal of Periodontal Research. 42 (6): 541–545. doi:10.1111/j.1600-0765.2007.00979.x. PMID 17956467.
  17. ^ Hong, Jiwon; Leung, Euphemia; Fraser, Alan G; Merriman, Tony R; Vishnu, Prakash; Krissansen, Geoffrey W (November 2007). "TLR2, TLR4 and TLR9 polymorphisms and Crohn's disease in a New Zealand Caucasian cohort". Journal of Gastroenterology and Hepatology. 22 (11): 1760–1766. doi:10.1111/j.1440-1746.2006.04727.x. PMID 17914947. S2CID 20973083.

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