lec 51.docx

Slide 2 The cytoskeleton has three types of protein filaments: 1. Intermediate filaments 2. Microtubles filaments 3. Actin filaments A diagram of different types of microtubules Description automatically generated Each type of filament has different mechanical properties Each filament Is m...

Slide 2 The cytoskeleton has three types of protein filaments: 1. Intermediate filaments 2. Microtubles filaments 3. Actin filaments A diagram of different types of microtubules Description automatically generated Each type of filament has different mechanical properties Each filament Is made of different protein These filaments are shown in the epithelial cells but exist in almost all animal cells Slide 3 Intermediate filaments are strong and rope like, made from long strands twisted together to provide tensile strength An electron micrograph shows that intermediate filaments are made of protein subunits Each protein subunit has a central rod domain with unstructured ends Each the rod domain is an extended a helical region allowing two proteins to from stable dimers by warping around each other in a coiled coil shape Two coiled coil dimers running in opposite direction come together to from a staggered tetramer  Slide 4 The dimers and tetramers are the soluble building blocks of intermediate filaments Tetramers line up side by side and then assemble to from the sina rope like intermediate filaments Diagram of a diagram of a structure Description automatically generated with medium confidence Slide 5 intermediate filaments are divided into four classes 1. Keratin filaments in epithelial cells 2. Vimentin and vimentin related filaments in connective tissue cells, muscle cells, and glial cells (supporting cells of the nervous system ) 3. Neurofilaments in nerve cells 4. Nuclear laminas, which strengthen in the nuclear envelope The first three types are found in the cytoplasm, while the fourth is found in the nucleus  Slide 6 - The nuclear lamina, made of lamins, breaks down and reforms during each cell division - During mitosis, the nuclear envelope breaks down and reform in the daughter cells - Cytoplasmic intermediate filaments also disassemble during mitosis - The disassembly and reassembly of the nuclear lamina are controlled by the phosphorylation (add phosphate group) and dephosphorylation (removing phosphate group ) of the lamins A diagram of a nuclear cell Description automatically generated Slide 7 - Phosphorlation by protein kinases changes the shape of lamins - This shape change weakens the bonds between lamin tetramers, causing the filaments to break a part - At the end of mitosis depjosphorylation by protein phosphatases allows the lamins to reassemble  Slide 8 - Microtubules are made from subunits called tubulin - Each tubulin subunit is a dimer made of two proteins a tuvulin and b tubulin - These two proteins are tightly bound together by noncovalent interactions A drawing of a cylinder with a needle and green circles Description automatically generated Slide 9 - Tubulin dimers stack together using noncovalent bonds to form the wall og the hollow cylindrical microtubule - The structure is made of 13 parallel protofilaments which are linear chains of tubulin dimers - The tubulin dimers alternate between a tubulin and b tubulin along protofilaments - Each protofilament has structural polarity with one being the b tubulin (plus end ) and the other the a tubulin (minus end)  Slide 10 - In animal cells the centrosome, located near the nucleus when the cell is not dividing, organizes microtubules that spread through the cytoplsama - The centrosome has a pair of centrioles surrounded by a protein matrix - The matrix contains many ring shaped structures made of y tubulin - Each y tubulin ring is a starting point for the growth of microtuble - Ab tubulin dimers add to the y tubulin ring in a specific direction, with the minus end anchored in the centrosome - Microtubules grow only at the plus end, which etends into cytoplasm A diagram of a cell Description automatically generated Slide 11 - After microtubule starts growing it usually extends from the organizing center for several minutes by adding ab tubulin dimers to the plus end - Suddenly the microtubule can start to shrink quickly by losing tubulin dimers from its plus end - It might shrink partially and then start growing again or it could disappear entirely and be replaced by a new microtubule growing from the same y tubulin ring - This process of swiching between growing (polymerization) and shrinking (depolymerization) is called dynamic instabililty  Slide 12 - A growing microtubule can be sopped from shrinking if its plus end is stabilized by attaching to another molecule or cell structure - This stabilization prevents the microtubule from deplolymerizing (breaking down) - If the microtubule is stabilized by the attaching to a structure far away in the cell, it can form a satble connection between that structure and the centrosome A diagram of a cell membrane Description automatically generated Slide 13 läs extra - The dynamic instability of microtubules is caused by tubulin dimers ability to hydrolyze GTP (break down GTP to GDP) - GTP hydrolysis controls the instability of microtubules - Tubulin dimers with GTP (red) bind tightly to each other, while those with GDP (dark green) don't bind strongly - Microtubules with fresh GTP bound tubulin dimers at their pus end tend to keep growing  Slide 14 LÄS EXTRA - Sometimes especially when the microtubule growth is slow the dimers in the GTP cap with hydrolyez GTP to GDP before new GTP bound dimers can attach - This causes the GTP cap to be lost - Dimers with GDP are less tightly bound so the protofilaments peel away from the plus end - As a result, the dimers are released and the microtubule shrinks Slide 15 - Most animal cells are polarized meaning one end of the cell is different from the other in structure of function - In nerve cells an axon extends from one end and dendrites from the other - In the axon all microtubules point in the same direction with their puls ends toward the axon terminals - These microtubules help transport organelles, vesicles and molecules either from the cell body to the axon terminals or the other way around  Slide 16 - Motor proteins that move along microtubules belong to two families 1. Kinesins usually move toward the plus end of a microtubule 2. Dyneins move toward the minus end - Both kinesins and dyneins are dimers with ATP binding heads and one tail - A diagram of a cell membrane Description automatically generated Slide 17 - The heads of motor proteins interact with microtubules in specific way, so the motor proteins attaches to the microtubules in only one direction - The tail of the motor proteins binds to other cell components like vecicles or organelles - this bindning determines the type of cargo the motor protein can transport -  Slide 18 - Cili move in a whip like motion to either move fluid over the cell surface or propel single cells through fluid - A cilium beats by repeating a cycle of movement, including a power stroke and a recovery stroke - In the fast power stroke the cilium is fully extended pushing fluid over the cell surface - Each cycle takes 0.1 to 0.2 scounds and creats force parallel to the cell surface A diagram of a power stroke Description automatically generated Slide 19 - Flagella like those on sperm and many protozoa are similar to cilia in structure nut are much longer - Flagella are designed to more the entrie cell rather then fluid across the cell surfave - They create length push the cell forward - The movement of single flagellum on a sperm cell was captured using stroboscopic lighting at 400 flashed per second  Slide 20 - The microtubule in cilia and flagella are different from those in the cytoplasm, arranged in a unique pattern - In a cross section of a cilium, nine pairs of doublet microtubules from ring around two single microtubules - This 9 + 2 arrangement is typical for nearly all eukaryotic cilia and flagella from protozoa human A diagram of a cell structure Description automatically generated Slide 21 - Cilia and flagella move by bending their core as microtubules slide against each other - Microtubules have accessory proteins along their length - Some proteins act cross links to hold the microtubule bundle together while others create the force needed for bending - In a cross section of flagellum nine outer microtubules have two rows of dynein molecules - Dynein heads look like arms that reach towards the neighbroing microtubules  Slide 22 READ MORE ABOUT IT - Ciliary dynein attaches its tail to one microtubule, and heads interact with a neighboring microtubule to create sliding force between them - The sliding force is converted into a bending motion due due to the links that hold the microtubule doublets together - A if dynein and the microtubules are separated from other parts of sperm flagellum and exposed at ATP, the microtubles slides against each other in a telescoping manner - B in an intact flagellum the doublets are tied together by flexible links, causing the system to produce bending instead of sliding Diagram of a double-sided slide Description automatically generated with medium confidence Slide 23 - Actin filaments work with many actin bidning proteins allowing them to perform various functions in cells - Actin filaments can form strong satble structures like microvilla in intestinal cells or small contractile bundles that act like tiny muscles in animal cell - They can also create temporary structures such as protrusions at the leading edge of a moving cell or the contractile ring that divides a cell during cell division - Actin based movements usually need motor protein called myosin  Slide 24 - A bare actin filament like microtubule without proteins, is unstable and can break down at both ends - If there are many free actin monomers the filaments grows quickly by adding monomers to both ends - At medium concentrations something interesting happens: monomers add to the plus end faster than atp is hydrolyzed faster than new monomers can added, causing the filaments to lose subunits - This creates a process where monomers move through the filaments from plus end to minus end called treadmilling - Both actin treadmillingand microtubule dynamic instability depends on hydrolysis of a bound nucleoside triphosphate control filaments length A diagram of a diagram of a treadmill Description automatically generated Slide 25 - In human blood cells a regular network of fibrous proteins including actin and spectrin filaments is attached to plasma membrane - This network provides support for the cells to maintain their flat disc like shape  Slide 26 - Cell crawling involves coodintaed changes in different parts of the cell - Three key processes essential for cell movement: 1. The cell pushes out protrusions at the front \*leading edge) 2. These protrusions stick to the surface the cell is crawling on 3. The rest of the cell pulls forward using these anchorage points - Actin polymerization pushes the plasma membrane forward creating new actin cortex regions - New anchorage points from at the bottom of the cell while the old ones are released at the back - This cycle repeats, allowing the cell to move step by step Slide 27 - The growth of actin filaments at the front (keading edges) of a cell is helped by actin binding proteins - Additional actin binding proteins help assemble the actin network at the front and disassemble it further back - This process pushes the lamellipodium (cell extension) forward  Slide 28 - Myosin I is found in all types of cells and has head and tail - The head binds to actin filaments and uses ATP to move by repeatlly attaching detaching and reattaching to the filaments - The head domain can move a vesicle along an actin filaments anchored to the plasma membrane - Myosin I can also bind to actin filaments in the cell cortex, pulling the plasma membrane into new shape - The head always moves toward the end of the actin filament A diagram of a cell membrane Description automatically generated Slide 29 - Muscle myosin is part of the myosin II subfamily where all members are dimers - Each myosin II molecule has two globular ATPase heads at one end and coiled coil tail at the other - Myosin II molecules cluster together through their collided coil tails forming a bipolar filament with heads projecting from both ends  Slide 30 - The myosin filment is like a double headed arrow with two sets of heads pointing in opposite directions - One set of myosin heads bind to actin filament and moves them in one direction while the other set binds to actin filaments and moves them in the opposite direction direction - This allow myosin filament to slide actin filaments that are oriented in opposite directions past each other A diagram of a cell cycle Description automatically generated Slide 31 - Skeletal muscle fibers are large multinucleated cells formed by the fusion of smaller cells - The nuclei from the fused cells are kept and lie just under the plasma membrane - Most of the cytoplasm consists of myofibrils which arw the muscle cells contractile element - Myofibrils are made of repeating units called sarcomeres each about 2.5 um long - The repeating pattern of sarcomeres give vertebrate myofibrils striped appearance  A close-up of a black and white pattern Description automatically generated Slide 32 - Sarcomeres are made up of two types of filaments: actin filaments and myosin filaments, which contain a muscle specific type of myosin II - The mysosin filaments (thick filaments) are located in the center of each sarcomere - The actin filaments (thin filaments) are thinner and extend from each end of the sarcomere - The actin filaments are anchored by their plus ends to a structure called Z disc - The minus ends of the actin filaments overlap with the ends of the myosin filaments  Slide 33 - An electron micrograph shows two myofibrils indicating the length of one sarcomere and the region where actin and myosin filaments overlap - A diagram od a sarcomere show how light and dark bands appear under a microscope - The Z discs at each end of sarcomere are attachment points for the plus ends of actin filaments - The thick filaments in the center of the sarcomere are made of many myosin II molecules A close-up of a microscope Description automatically generated Slide 34 - Muscle contraction happens when all the sarcomeres in a muscle cell shorten at the same time - The shortning is due actin filaments sliding past myosin filaments, without changing the length of either filaments - The slidning is caused by myosin head projecting from the myosin filaments and interacting with actin filaments - When a muscle is stimulated the myosin heads move alone the actin filaments through repeated cycle attachment and detachment  Slide 35 read more - The interaction between myosin and actin filaments that generates force happens only when the skeletal muscle gets signal from a motor nerve - The nerve releases a neurotransmitter which trigger an action potential in the muscle cells plasma membrane - The electrical signal qucickly spreads into T tubules which are tubes that extend and inward from the plasma membrane around each myofibril - This signal is passed to the sarcoplasmic reticulum a network of flattened vesicles surrounding each myofibril - The sarcoplamatic reticulum is a specialized region of the endoplasmic reticulumin the muscle cells A close-up of a cell Description automatically generated Slide 36 - The sarcoplasmic reticulum holds a very high concentration of calcium ions Ca2+ - When the muscle receives an electrical signal Ca2+ is released into the cytosol through ion channels in the sarcoplasmic reticulum - These ions channels open in response to avoltage change across the plasma membrane and T tubules - A Ca2+ release channel in the sarcoplasmic reticulum is activated by a voltage gated channel in the T tubule membrane - The release of Ca2+ into the cytosol triggers skeletal muscle contraction  Slide 37 - In muscles an increase in Ca2+ in the cytosol activates a molecular switch made of special proteins that are closely associated with actin filaments - One of these proteins is tropomyosin a rod shaped molecule that binds in the groove of the actin helix and precents myosin heads from attaching ti the actin filaments - Another protein is troponin a complex that includes a Ca2+ sensitive protein linked to the end of tropomyosin A diagram of a cell structure Description automatically generated Slide 38 - When Ca2+ concentration increases in the cytosol, Ca2 binds to troponin changing its shape - This shape change causes tropomyosin to move slightly - The movement allow myosin heads to bind to actin filaments starting muscle contraction  Slide 39 - The signal from the plasma membrane reaches every sarcomere in the cell within milliseconds causing all the myofibrils to contract at the same time - The increase in Ca2 is temporary because after the nerve signal ends Ca2 is quickly pumped back into the sarcoplasmic reticulum by Ca2 pumps in its membrane - Once the Ca2 levels return to normal troponin and tropomyosin move to their original positions - The movement blocks myosin from binding to actin filaments ending muscle contraction A diagram of a motor neuron Description automatically generated Slide 40 - Smooth muscle found in organs like the stomach, intestines, uterus, and arteries, contract slowly and involuntarily - The activation mechanism is smooth muscle is slower because enzyems must reach the myosin heads to phosphorylate and dephosphorylate them - Unlike skeletal muscle smooth muscle can be activated by many different signals including adrenaline serotonin, prostaglandins and other signal molecules.