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Plasma membrane Ca2+ ATPase

From Wikipedia, the free encyclopedia

Rendered image of the Ca2+ pump

The plasma membrane Ca2+ ATPase (PMCA) is a transport protein in the plasma membrane of cells that functions as a calcium pump to remove calcium (Ca2+) from the cell. PMCA function is vital for regulating the amount of Ca2+ within all eukaryotic cells.[1][2] There is a very large transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into cells, yet it is very important that they maintain low concentrations of Ca2+ for proper cell signalling. Thus, it is necessary for cells to employ ion pumps to remove the Ca2+.[3] The PMCA and the sodium calcium exchanger (NCX) are together the main regulators of intracellular Ca2+ concentrations.[2] Since it transports Ca2+ into the extracellular space, the PMCA is also an important regulator of the calcium concentration in the extracellular space.[4]

PMCAs belong to the family of P-type primary ion transport ATPases which form aspartyl phosphate intermediates.[2]

Various forms of PMCA are expressed in different tissues, including the brain.[5]

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Transcription

Oh, hey! I didn't see you up there. How long have you been waiting in this line? I've been here for like 15 minutes and it's freaking freezing out here I mean, whose banana do you gotta peel in order to get into this club? Well, while we're here I guess this might not be a bad time to continue our discussion about cells. Because cells, like nightclubs, have to be selectively permeable. They can only work if they let in the stuff that they need and they kick out the stuff that they don't need like trash and ridiculously drunk people and Justin Bieber fans. No matter what stuff it is it has to pass through the cell's membrane. Some things can pass really easily into cells without a lot of help, like water or oxygen. But a lot of other things that they need, like sugar, other nutrients, signaling molecules or steroids they can't get in or it will take a really long time for them to do it. Yeah. I can relate. Today we're going to be talking about how substances move through cell membranes, which is happening all the time, including right now, in me and right now, in you. And this is vital to all life, because it's not just how cells acquire what they need and get rid of what they don't, it's also how cells communicate with one another. Different materials have different ways of crossing the cell membrane. And there are basically two categories of ways: there's active transport and there's passive transport. Passive transport doesn't require any energy, which is great, because important things like oxygen and water can use this to get into cells really easily. And they do this through what we call diffusion. Let's say I'm finally in this show, and I'm in the show with my brother John. Some of you know my brother John, and I love him, but he uh... He's not a big fan of people. I mean he likes people. He doesn't like big crowds. Being parts of big crowds and people standing nearby him, breathing on him, touching him accidentally and that sort of thing Because John's with me at the show, we're hanging out with all of our friends near the stage. But then he starts moving further and further from the stage so he doesn't get a bunch of hipsters invading his space. That's basically what diffusion is. If everyone in the club were John Green they would try and get as much space between all of them as possible until it was a uniform mass of John Greens throughout the club. When oxygen gets crowded, it finds places that are less crowded and moves into those spaces. When water gets crowded, it does the same thing and moves to where there is less water. When water does this across a membrane, it's a kind of diffusion called osmosis. This is how your cells regulate their water content. Not only does this apply to water itself, which as we've discussed is the world's best solvent. You're going to learn more about water in our water episode. It also works with water that contains dissolved materials, or solutions, like salt water, or sugar water, or booze, which is just a solution of ethanol in water. If the concentration of a solution is higher inside a cell than it is outside of the cell, then that solution is called hypertonic Like Powerthirst, it's got everything packed into it! And if the concentration inside of the cell is lower than outside of the cell, it's called hypotonic. Which is sort of a sad version of hypertonic. Like with Charlie Sheen: we don't want the crazy, manic Charlie Sheen and we don't like the super sad, depressed Charlie Sheen. We want the "in the middle" Charlie Sheen who can just make us laugh and be happy. And that is the state that water concentrations are constantly seeking. It's called isotonic. When the concentration is the same on both sides, outside and in. And this works in real life! We can actually show it to you. This vase is full of fresh water. And we also have a sausage casing, which is actually made of cellulose, and inside of that we have salt water. We've dyed it so that you can see it move through the casing, which is acting as our membrane. This time lapse shows how over a few hours, the salt water diffuses into the pure water. It'll keep diffusing until the concentration of salt in the water is the same inside the membrane as outside. When water does this, attempting to become isotonic, it's called moving across it's concentration gradient. Most of my cells right now are bathed in a solution that has the same concentration as inside of them, and this is important. For example, if you took one of my red blood cells and put it in a glass of pure water, it would be so hypertonic so much stuff would be in the cell compared to outside the cell that water would rush into the red blood cell and it would literally explode. So, we don't want that! But if the concentration of my blood plasma were too high, water would rush out of my cell, and it would shrivel up and be useless. That's why your kidneys are constantly on the job, regulating the concentration of your blood plasma to keep it isotonic. Now, water can permeate a membrane without any help, but it's not particularly easy. As we discussed in the last episode, some membranes are made out of phospholipids, and the phospholipid bilayer is hydrophilic, or water-loving, on the outside and hydrophobic, or water-hating, on the inside. So water molecules have a hard time passing through these layers because they get stuck at that nonpolar, hydrophobic core. That is where the channel proteins come in. They allow passage of stuff like water and ions without using any energy. They straddle the width of the membrane and inside they have channels that are hydrophilic, which draws the water through. The proteins that are specifically for channeling water are called aquaporins, and each one can pass 3 billion water molecules a second! It makes me have to pee just thinking about it. Things like oxygen and water, that cells need constantly, they can get into the cell without any energy necessary but most chemicals use what's called active transport. This is especially useful if you want to move something in the opposite direction of its concentration gradient, from a low concentration to a high concentration. So, say we're back at that show, and I'm keeping company with John who's being all antisocial in his polite and charming way, but after half a beer and an argument about who the was the best Dr. Who. I want to get back to my friends across the crowded bar. So I transport myself against the concentration gradient of humans, spending a lot of energy, dodging stomping feet, throwing an elbow, to get to them. THAT is high energy transport! In a cell, getting the energy necessary to do pretty much anything, including moving something the wrong direction across it's concentration gradient, requires ATP. ATP or adenosine tri-phosphate You just want to replay that over and over again until it just rolls off the tongue because it's one of the most important chemicals that you will ever, ever ever hear about. Adenosine tri-phosphate, ATP. If our bodies were America, ATP would be credit cards It's such an important form of information currency that we're going to do an entire separate episode about it, which will be here, when we've done it. But for now, here's what you need to know. When a cell requires active transport, it basically has to pay a fee, in the form of ATP, to a transport protein. A particularly important kind of freakin' sweet transport protein is called the sodium-potassium pump. Most cells have them, but they're especially vital to cells that need lots of energy, like muscle cells and brain cells. Oh! Biolo-graphy! It's my favorite part of the show. The sodium-potassium pump was discovered in the 1950s by a Danish medical doctor named Jens Christian Skou, who was studying how anesthetics work on membranes. He noticed that there was a protein in cell membranes that could pump sodium out of a cell. And the way he got to know this pump was by studying the nerves of crabs, because crab nerves are huge compared to humans' nerves and are easier to dissect and observe. But crabs are still small, so he needed a lot of them. He struck a deal with a local fisherman and, over the years, studied approximately 25,000 crabs, each of which he boiled to study their fresh nerve fibers. He published his findings on the sodium-potassium pump in 1957 and in the meantime became known for the distinct odor that filled the halls of the Department of Physiology at the university where he worked. Forty years after making his discovery, Skou was awarded the Nobel Prize in Chemistry. And here's what he taught us: Turns out these pumps work against two gradients at the same time. One is the concentration gradient, and the other is an electrochemical gradient. That's the difference in electrical charge on either side of a cell's membrane. So the nerve cells that Skou was studying, like the nerve cells in your brain, typically have a negative charge inside relative to the outside. They also usually have a low concentration of sodium ions inside. The pump works against both of these conditions, collecting three positively-charged sodium ions and pushing them out into the positively charged, sodium ion-rich environment. To get the energy to do this, the protein pump breaks up a molecule of ATP. ATP, adenosine tri-phosphate, is an adenosine molecule with three phosphate groups attached to it, but when ATP connects with the protein pump, an enzyme breaks the covalent bond of one of those phosphates in a burst of excitement and energy. This split releases enough energy to change the shape of the pump so it "opens" outward and releases the three sodium ions. This new shape also makes it a good fit for potassium ions that are outside the cell, so the pump lets two of those in. So what you end up with is a nerve cell that is literally and metaphorically charged. It has all those sodium ions waiting outside with this intense desire to get inside of the cell. And when something triggers the nerve cell, it lets all of those in. And that gives the nerve cell a bunch of electrochemical energy which it can then use to let you feel things, or touch, or smell, or taste, or have a thought. There is still yet another way that stuff gets inside of cells, and this also requires energy. It's also a form of active transport. It's called vesicular transport, and the heavy lifting is done by vesicles, which are tiny sacs made of phospholipids just like the cell membrane. This kind of active transport is also called cytosis, from the Greek for "cell action" When vesicles transport materials outside of a cell it's called exocytosis, or outside cell action. A great example of this is going on in your brain right now. It's how your nerve cells release neurotransmitters. You've heard of neurotransmitters. They are very important in helping you feel different ways. Like dopamine and serotonin. After neurotransmitters are synthesized and packaged into vesicles, they're transported until the vesicle reaches the membrane. When that happens, their two bilayers rearrange so that they fuse. Then the neurotransmitter spills out and -- now I remember where I left my keys! Now just play that process in reverse and you'll see how material gets inside a cell. That's endocytosis. There are three different ways that this happens. My personal favorite is phagocytosis, and the awesome there begins with the fact that that name itself means DEVOURING CELL ACTION! Check this out. So this particle outside here is some dangerous bacterium in your body. And this is a white blood cell. Chemical receptors on the blood cell membrane detect this punk invader and attach to it, actually reaching out around it and engulfing it. Then the membrane forms a vesicle to carry it inside, where it lays a total, unholy beatdown on it with enzymes and other cool weapons. Pinocytosis, or drinking action, is very simIlar to phagocytosis, except instead of surrounding whole particles, it surrounds things that have already been dissolved. Here the membrane just folds in a little to form the beginning of a channel and then pinches off to form a vesicle that holds the fluid. Most of your cells are doing this right now, because it's how our cells absorb nutrients. But what if a cell needs something that only occurs in very small concentrations? That's when cells use clusters of specialized receptor proteins in the membrane that form a vesicle when receptors connect with the molecule that they're looking for. For example, your cells have specialized cholesterol receptors that allow you to absorb cholesterol; if those receptors don't work, which can happen with some genetic conditions, cholesterol is left to float around in your blood and eventually causes heart disease. So that's just one of many reasons to appreciate what's called receptor-mediated endocytosis. Ah! Hey, glad you made it in too! Now comes review time. You can click on any of these links and go back to the part of the video where I talk about that thing if you are at all confused. And you may be. This is totally, pretty complicated stuff we're dealing with right now, so you just go ahead and watch all that. And if you have any questions, of course, we'll be down below in the comments and on Twitter and Facebook as well and we'll see you next time.

Actions

The pump is powered by the hydrolysis of adenosine triphosphate (ATP), with a stoichiometry of one Ca2+ ion removed for each molecule of ATP hydrolysed. It binds tightly to Ca2+ ions (has a high affinity, with a Km of 100 to 200 nM) but does not remove Ca2+ at a very fast rate.[6] This is in contrast to the NCX, which has a low affinity and a high capacity. Thus, the PMCA is effective at binding Ca2+ even when its concentrations within the cell are very low, so it is suited for maintaining Ca2+ at its normally very low levels.[3] Calcium is an important second messenger, so its levels must be kept low in cells to prevent noise and keep signalling accurate.[7] The NCX is better suited for removing large amounts of Ca2+ quickly, as is needed in neurons after an action potential. Thus the activities of the two types of pump complement each other.

The PMCA functions in a similar manner to other p-type ion pumps.[3] ATP transfers a phosphate to the PMCA, which forms a phosphorylated intermediate.[3]

Ca2+/calmodulin binds and further activates the PMCA, increasing the affinity of the protein's Ca2+-binding site 20 to 30 times.[6] Calmodulin also increases the rate at which the pump extrudes Ca2+ from the cell, possibly up to tenfold.[3]

In brain tissue, it has been postulated that certain types of PMCA are important for regulating synaptic activity, since the PMCA is involved in regulating the amount of calcium within the cell at the synapse,[5] and Ca2+ is involved in release of synaptic vesicles. Additionally, it has been shown that PMCA activity is modulated and partly powered by glycolysis in neuronal somata and dendrites.[8] Presumably, it is due to PMCA proximity to glucose transporters in the plasma membrane.

Structure

The structure of the PMCA is similar to that of the SERCA calcium pumps, which are responsible for removing calcium from the cytoplasm into the lumen of the sarcoplasmic reticulum.[2] Calcium tends to have a slightly lower affinity for PMCA pumps than for SERCA pumps.[9] It is thought that the PMCA pump has 10 segments that cross the plasma membrane, with both C and N termini on the inside of the cell.[2] At the C terminus, there is a long "tail" of between 70 and 200 amino acids in length.[2] This tail is thought to be responsible for regulation of the pump.[2] PMCA pumps have a molecular mass of around 140 kDa.[10]

Isoforms

There are four isoforms of PMCA, called PMCA 1 through 4.[5]

Each isoform is coded by a different gene and is expressed in different areas of the body.[5] Alternate splicing of the mRNA transcripts of these genes results in different subtypes of these isoforms.[2] Over 20 splice variants have been identified so far.[2]

Three PMCA isoforms, PMCA1, PMCA2, and PMCA3, occur in the brain in varying distributions.[6] PMCA1 is ubiquitous throughout all tissues in humans, and without it embryos do not survive.[4] Lack of PMCA4, which is also very common in many tissues, is survivable, but leads to infertility in males.[4] PMCA types 2 and 3 are activated more quickly and are, therefore, better suited to excitable cell types such as those in nervous and muscle tissue, which experiences large influxes of Ca2+ when excited.[5] PMCA types 1, 2, and 4 have been found in glial cells called astrocytes in mammals, though it was previously thought that only the NCX was present in glia.[11] Astrocytes help to maintain ionic balance in the extracellular space in the brain.

Knock-out of PMCA2 causes inner ear problems, including hearing loss and problems with balance.[12]

PMCA4 exists in caveolae.[12] Isoform PMCA4b interacts with nitric oxide synthase and reduces synthesis of nitric oxide by that enzyme.[12]

PMCA isoform 4 has a molecular weight of 134,683, calculated from its sequence.[13] This is in good agreement with the results of SDS gel electrophoresis.[14]

Pathology

When the PMCA fails to function properly, disease can result. Improperly functioning PMCA proteins have been found associated with conditions such as sensorineural deafness, diabetes, and hypertension.[4]

In excitotoxicity, a process in which excessive amounts of the neurotransmitter glutamate overactivate neurons, resulting in excessive influx of Ca2+ into cells, the activity of the PMCA may be insufficient to remove the excess Ca2+.

In breast tissue, mammary epithelial cells express PMCA2, which transports calcium across the apical surface of the cells into milk. PMCA2 expression falls on weaning, leading to calcium-induced apoptosis and mammary gland involution. Persistent PMCA2 expression in certain breast cancers lowers calcium levels inside malignant cells, allowing them to avoid apoptosis. These tumors are also usually positive for the HER2 protein, tend to involve the lymph nodes, and are more common among young women, which could help explain their worse prognosis compared with postmenopausal women.[15]

Curcumin can bind to the PMCA, inducing a conformational change that prevents ATP from binding.[16]

History

PMCAs were first discovered in the 1960s in the membranes of red blood cells.[2] The presence of an ATPase was discovered in the membranes in 1961, and then in 1966 it was discovered that these ATPases pump Ca2+ out of the cytosol.[3]

PMCA was first purified from red blood cell membranes in 1979.[17][18]

References

  1. ^ Jensen, Thomas P.; Buckby, Lucy E.; Empson, Ruth M. (2004). "Expression of plasma membrane Ca2+ ATPase family members and associated synaptic proteins in acute and cultured organotypic hippocampal slices from rat". Developmental Brain Research. 152 (2): 129–136. doi:10.1016/j.devbrainres.2004.06.004. PMID 15351500.Closed access icon
  2. ^ a b c d e f g h i j Strehler, Emanuel E.; Zacharias, David A. (2001). "Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps". Physiol. Rev. 81 (1): 21–50. doi:10.1152/physrev.2001.81.1.21. PMID 11152753. S2CID 9062253.Open access icon
  3. ^ a b c d e f Carafoli, E. (1991). "Calcium pump of the plasma membrane". Physiol. Rev. 71 (1): 129–153. doi:10.1152/physrev.1991.71.1.129. PMID 1986387.Closed access icon
  4. ^ a b c d Talarico, Ernest F. Jr.; Kennedy, Brian G.; Marfurt, Carl F.; Loeffler, Karin U.; Mangini, Nancy J. (2005). "Expression and immunolocalization of plasma membrane calcium ATPase isoforms in human corneal epithelium". Mol. Vis. 11: 169–178. PMID 15765049. Retrieved 2013-12-25.Open access icon
  5. ^ a b c d e Jensen, Thomas P.; Filoteo, Adelaida G.; Knopfel, Thomas; Empson, Ruth M. (2006). "Pre-synaptic plasma membrane isoform 2a regulates excitatory synaptic transmission in rat hippocampal CA3". J. Physiol. 579 (1): 85–99. doi:10.1113/jphysiol.2006.123901. PMC 2075377. PMID 17170045. Retrieved 2007-01-13.Open access icon
  6. ^ a b c Albers, R. Wayne; Siegel, George J. (1999). "5. Membrane Transport". In Siegel, George J.; et al. (eds.). Basic Neurochemistry: Molecular, Cellular, and Medical Aspects (6th ed.). Philadelphia: Lippincott-Raven. ATP-Dependent Ca2+ Pumps. ISBN 978-0-397-51820-3. OCLC 39013748. Retrieved 2013-12-25.Open access icon
  7. ^ Burette, Alain; Weinberg, Richard J. (February 2007). "Perisynaptic organization of plasma membrane calcium pumps in cerebellar cortex". J. Comp. Neurol. 500 (6) (published 2006-12-20): 1127–1135. doi:10.1002/cne.21237. PMID 17183553. S2CID 22110231.Closed access icon
  8. ^ Ivannikov, Maxim V.; Sugimori, Mutsuyuki; Llinás, Rodolfo R. (2010). "Calcium clearance and its energy requirements in cerebellar neurons". Cell Calcium. 47 (6): 507–513. doi:10.1016/j.ceca.2010.04.004. PMC 2900537. PMID 20510449.Closed access icon
  9. ^ Lopez, Jose R.; Allen, Paul D. (2012-01-01), Hill, Joseph A.; Olson, Eric N. (eds.), "Chapter 56 - Control of Resting Ca2+ Concentration in Skeletal Muscle", Muscle, Boston/Waltham: Academic Press, pp. 801–810, doi:10.1016/b978-0-12-381510-1.00056-9, ISBN 978-0-12-381510-1, retrieved 2020-11-08
  10. ^ Edes, Istvan; Kranias, Evangelia G. (1995-01-01), Sperelakis, NICHOLAS (ed.), "13 - Ca2+-ATPases", Cell Physiology Source Book, Academic Press, pp. 156–165, doi:10.1016/b978-0-12-656970-4.50019-1, ISBN 978-0-12-656970-4, retrieved 2020-11-08
  11. ^ Fresu, Luigia; Dehpour, Ahmed; Genazzani, Armando A.; Carafoli, Ernesto; Guerini, Danilo (November 1999). "Plasma membrane calcium ATPase isoforms in astrocytes". Glia. 28 (2) (published 1999-10-22): 150–155. doi:10.1002/(SICI)1098-1136(199911)28:2<150::AID-GLIA6>3.0.CO;2-7. PMID 10533058. S2CID 44343760.Closed access icon
  12. ^ a b c Schuh, Kai; Uldrijan, Stjepan; Telkamp, Myriam; Röthlein, Nicola; Neyses, Ludwig (2001). "The plasmamembrane calmodulin–dependent calcium pump : a major regulator of nitric oxide synthase I". J. Cell Biol. 155 (2): 201–205. doi:10.1083/jcb.200104131. PMC 2198825. PMID 11591728.Open access icon
  13. ^ Verma, Anil K.; Filoteo, Adelaida G.; Stanford, David R.; Wieben, Eric D.; Penniston, John T. (1988). "Complete Primary Structure of a Human Plasma Membrane Ca2+ Pump". J. Biol. Chem. 263 (28): 14152–14159. doi:10.1016/S0021-9258(18)68198-0. PMID 2844759. Retrieved 2013-12-25.Open access icon
  14. ^ Graf, Ernst; Verma, Anil K.; Gorski, Jeffrey P.; Lopaschuk, Gary; Niggli, Verena; Zurini, Mauro; Carafoli, E.; Penniston, John T. (1982). "Molecular Properties of Calcium-Pumping ATPase from Human Erythrocytes". Biochemistry. 21 (18): 4511–4516. doi:10.1021/bi00261a049. PMID 6215062.Closed access icon
  15. ^ VanHouten, Joshua; Sullivan, Catherine; Bazinet, Caroline; Ryoo, Tom; Camp, Robert; Rimm, David L.; Chung, Gina; Wysolmerski, John (2010-06-22). "PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer". Proc. Natl. Acad. Sci. U.S.A. 107 (25) (published 2010-06-04): 11405–11410. Bibcode:2010PNAS..10711405V. doi:10.1073/pnas.0911186107. PMC 2895115. PMID 20534448.Open access icon
  16. ^ Shehzad, Adeeb; Shahzad, Raheem; Lee, Young Sup (2014-01-01), Bathaie, S. Zahra; Tamanoi, Fuyuhiko (eds.), "Chapter Eight - Curcumin: A Potent Modulator of Multiple Enzymes in Multiple Cancers", The Enzymes, Natural Products and Cancer Signaling: Isoprenoids, Polyphenols and Flavonoids, 36, Academic Press: 149–174, doi:10.1016/b978-0-12-802215-3.00008-2, PMID 27102703, retrieved 2020-11-08
  17. ^ Niggli, Verena; Penniston, John T.; Carafoli, Ernesto (1979). "Purification of the (Ca2+-Mg2+) ATPase from Human Erythrocyte Membranes using a Calmodulin Affinity Column". J. Biol. Chem. 254 (20): 9955–9958. doi:10.1016/S0021-9258(19)86652-8. PMID 158595. Retrieved 2013-12-25.Open access icon.
  18. ^ Penniston, John T.; Gfiloteo, Adelaida; McDonough, Carol S.; Carafoli, Ernesto (1988). "Purification Reconstitution and Regulation of Plasma Membrane Ca2+ Pumps". Methods Enzymol. 157 (27): 340–351. doi:10.1016/0076-6879(88)57089-1. PMID 2976465.Closed access icon.

External links

This page was last edited on 7 November 2023, at 23:01
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