TOPIC 6

to our next topic which is stable 

Muscle cells and myosin motors, 

in tems of stbale actins trucutre, these actin structures that preseint for a long duration.  almost all of these trcutre have actin bidning protein these are protien aht bind to two actinfilemts and they bind to two simultanously to make a higher order actin network. There are protiens known as adaptor protien and they bind to actin filmetns to either membrane or membran bound protien, so adaptor protein connect the actin cyrtoskelogn to the plasme membrane or toher memrbane, if the cytoskleton is going to dictat the shape foteh cell, and the palsma membra is outisde skin of the cell  u will want to connect those two things so they are physcailly integrated.  

microvilli , there are some cell that have microvilin, and what the microivli do is they are these projections on one side of the cell that effectily increase the sruface area on the inside of the cell. these cells are going to take up nutrients and the bigger suface are the better. they are oging to have thei rplus ends at the top and the minus ends down the south, u can do expiemtn with t s1 head and ask which direction theyre pointing

the acitn filemtn extend down beyon the microvilis int othe cells where they are anchored, the filmetns are capped . we want them to be at a particular elngth.and we want them to be stable and presist as long as the cell is aorund so we cap the ends.  so the ends are not perafectly capped and some nomers are lost fromthe plus end and then regained from the plus end. so althouhg theyre caped in paritcular length there can be some uncapping and there can be some loss and then regain athe plus end,  the mins are stably capped . there are going to be actin bidning pprotiens that connec thte filetns to the memrbane and eachother, 

there are goung to be dif types of actin binding proteins, theyse can bind to two dif actin filaments at a time and they can rrange the filemtns into dif types of bundcles with dif spacing between the filmetns.  so like a contractil bundle that is part of muslce ocntraction. there are mysoin motor protien that move along the filmetns and cause contraction, so  acitn binding protien, alpha actinin, will space the actin filaments apart in a precisce manner in which the motor protein can et in and move along the filemtns to cause contraction.  in places like micrvil we have parallel bundlces in which the actin filmetns are closer together. so there are dif actin bind protiens that bidn to two filemtsn . these things do not contract, mysoin motors do not move along these bundles that are found in microvilin.  they are clsoe noguh that u cant get the musoin motor proetin in there. the mysoin are exlcuded by tight packing. 

diif actin bidnni protien allow the cell to arrange filemtns in dif types of buncles and network strucutre,  higher order structure with dif aragngment of filemts and dif spcaicng of filemtsn so they become spexalied to do a task. 

actin filmets are in brown and actin bidnign protein in blue that are conecting the iflmetns - look at how precise the filemtsn are 

proteins involved  = fembrin which is found in micrvili and ohter places that arrange the aitn filemtsn in parllel bundles with tight psacing

alpha actinin that is in stress fibers and muscle cells and make parllel bundles and spaced wider so mysoin motors can ge int here to allow  contraction and movment

Spectrin is a longer protein its actually a dimer. so what in the image what is in blue is the actin bidning domains so many of these things are eighter hav etwo acting bidnign odmains or are in idmers  in which the bidnign domain faces inopposite direction and that allwos them to bidn tow actin filemtsn at the same time causing parllel. 

filament - is much larger and they reach out and grab onto two actinfilemtsn and they arel ong and dont arrange in paralle bundles and grab filemtsn in dif way and make networks of filemtns. 

there can be more than one type of arrangement. there are situation wher eu have mutlipl protiens bound. 

so red blood cells - thsi si sort of another sitution in which nature has solved problem that u never knew u had - problem is that these red bloo cell shave a particualr diameter and in the blood systme u have arties and arterioles and vien and venules, arties and artierls ar the vessel in which the heart sends blood out into, and the viens are where the blood comes back ot the heart , betewen the arties and the viens connectin the two are cappilaries.  they are theinties blood vessles and the issue here is that the dimaeter and of the cappilers is smaller tha n the dimater of the red bloo cells. so the redbloo cells have to squeeze to go trhough the capillareis. they get squished down. they have a toriod shape befor ethey enteir the capilary and then they squish donw to a dif shape and whne they come back from the other side of the capilary they are back to the toiroid shape. the cytoskeling in redb blooc els is a serios of springs that hold the cell in shape, and pop back out and retunrs it back to its shape. there is a hub and psokes that emenate form the hub. 

these thigns that can bend, they can fold together and when they come out the other side they pop back to its og shape. the proteins that act as a spring is anchring and spectrin. Anchoring is the ball and ankyrinis the linear shape. actin is a hub . so the hub is a short actin filmtsn that binds the springs. they dont play a structureal role, its a hub which ankryin and spectrin are bound that allow this spring typ eof cytoskelong that allow the blood cells to collapse and then popback up .  

anothe rset of proteins known as the ERm family of pretions, named after the first three family memenrs Ezrin, radixin and moessin. dont need to memorize those names just the ERM family . this set of protein connec the actin cytoskelton to the memrbane 

one end of the set of three protien binds ot he actin filemtsn and then the other side of thsi chain binds ot the proteins that are associated with theplasma memrbane.  so its just connects the acint cytsoklion to the memrbaen , proteins that do this that connect the acitn cytoskelton to the memrbane are called adaptor proteins. 

there are dif set of adaptorer prtoeins that conenct the mcirtubule cytoskelon to the membrane.  Dif erm fmaily members conenct dif types of actins tructure to dif memrbeanes.  not jsut the plasma membrenae. 

idea that actin is a conservced protein and it sequence varies not much between organism. so actin in human is 90% or more identily to actin in fruit flies. not all protiens have that property some propety. some prtoisn vayr a lot from the veriso that sin fruit flies to the version that is in humans. so one question si that what is the properties of proteins that are conserved. one answer is that actin interacts with dif protiens, they interact with mscuel cells, micrvili, leading edge, sometiems in buncles, soemtiemes they move vescles, lysteiral, they are strucutres, there is process like secretion. so there are proteins involed in seceriton eacho f which touches actin somwerhe along its elgnt. 

binding site for some of these proteins, 

one protein binds to a part in actin, and then another protien binds to wher ethe yelliw, third binds ot hte blue area, another protein to the red, andother in black. the bottom line is that there are few amino acids on the sruface of  actin that do not interact withs oem proteins, as a reuslt if u muate any amino acid on the sruface of actin, youre going to dirupt the bidning of one protein or another. if u change an amino acids that interal thats not on the surface and you disrup thte ofling of actin, your going to dirutpthe role of acint in at least one process and possibly all process so the bottom line is that bc actin interacts with whole bunch of dif protien that changin any maino acid  is lliley to screw up one fucniton or another. and so one of the reason tha citn is highly consvered is bc almost any muation screws up one frunciton or another.  

why are protien and actin in particular highly consvered in eovltion. answer is bc thyer eessential. if u screw up essential fucniton then youre screwed. 

however actin has many fucniton and interacts iwth many bidngin protiens and so even mtaution that dont act as null alells that you still prudce actin , actin may still work fine in 20 fucntion but not in 4 funcitons. a lto of protein that are highly consvered bind many dif proteins as well as have an essential fucniton and are involed in other dif funcitons.   

histones are consvered . hsitone tails are going to get modified in dif was, and these modifiation can compact or decompat the chormtin, but how? we have modications and the modifation is going to bind difrente protiens, so histone tails that is methylation lysine 4 bidns protien x and aceytalted on lysein 4 will bidng protien y. So just like acitn here having lots of proeitns and being hihgly conserved, we have the histones whihc are highly conserved which are also bidng lots of dif protiens.  so converstiaont of preotins during evolutions is a result of dif preocesses , dif ocmbtaiton of preoces in dif protiens. 

example - invention of somethign is rare, we invented two kidsn of filements that motor proetin move on, actin and mcirotubuesl, but then we can adapt actin filmetns to do a whole bunch of thigns so they dont just act as a place where motors move. the leading edge or things like listeria .

complex suprise, when ppl disovvered that actin and actin family member ARP4, actin related protien four, act 1 is the gene in yeast tha encodes acitn, so this acitn itself nad an actin family member.  these are structral subunts of chormatin remodling complex.  

remmerb tath chormatin remodling compelsx are proetin compelx that can moves histone out of the way. and it urns out that those have many di fpreoitns. so in pink there are subutnso fo chroamtin remodling complex, so its got a bunch of subunots two of which are these actin and an actin family member.  hereas anotehr chormtin remodling compelx thats got a bunch of subuntsi but again actin and the acitn family membres are subuntsi and hers a thign one and so these sub choramtin remodlin complexes are convserved from yeast to humans andso actin ebcame a part of these chormatin remodling complexs back wehnw e shared a common ancestor with years  or even earlier in evoltuoinary time. and so actin has been aroudn along time, and actin has been adapted to a wide rand og dif funciton foa long time. 

Thsi is not a actinf ilemts, these are two family memrbns that act as a dimer that are requied to build to the strcutre of the chormt remodling ompelx. very surpirisng use of actin. 

so actin family membrs are used to build a chormatin remodling complez. convserved from yeast to humans. 

end of 6 

—