Cell Biology 2

  1. Rhodopsin
    • A G-protein-coupled light receptor that controls non-color vision in animals
    • Rhodopsin activates the G protein transducin which activates the intracellular signaling cascade which causes cation channels to close in photoreceptor cells
    • Changes the voltage across the membrane which alters the neurotransmitter release
    • When light is dim, amplification of the signal is increased
    • When light is abundant, the signal cascade adapts and reduces the amplification so that the photoreceptor cells are not overwhelmed
  2. Rhodopsin refined
    Rhodopsin activates G protein transducin which activates intracellular cascade of ion channels to close photoreceptor cells
  3. Receptor tyrosine kinase (RTKs)
    • Contact causes phosphorylation of other tail
    • Phosphorylation causes signaling proteins to be activated
    • Protein tyrosine phosphatase removes phosphates (terminates the signal)
  4. Ethylene receptors in plants
    • Dimeric transmembrane proteins
    • Empty receptor is active (activates a protein kinase which shuts off ethylene-responsive genes
  5. Hormones
    Send a general communication throughout the body and are produced by endocrine cells
  6. Signal transduction
    Message converted from one form to another
  7. Paracrine signals
    • Diffuse locally through the extracellular fluid, and stay within the region from which they're secreted (inflammation of wounds)
    • Act as local mediators on nearby cells
  8. Neuronal signaling
    • Can travel long distance, but signal is picked up by individual cells through their own lines
    • Delivered quickly and specifically to individual target cells through private lines
  9. Synapse
    Junctions where electrical signals are converted into chemical signal (neurotransmitter) which diffuses across the gap
  10. Contact-dependent
    • Very short range and done through physical contact of signal molecules and receptors in plasma membrane
    • In embryonic development, contact-dependent cell signaling inhibits neighboring cells from becoming specialized in the same way as cell signaling
  11. What happens to a cell in the absence of any other signaling?
    Most animal cells are programmed to kill themselves
  12. Target protein
    • Also known as a receptor
    • Activated by only one type of signal
  13. Signaling cascades
    • Receptor receives an external signal and generates a new intracellular signal in response
    • The internal signal is passed on until a response is generated
  14. Function of signaling cascade
    • They transform, or transduce the signal into a molecular form suitable for passing the signal along or stimulating a response
    • Amplify the signal receieved, making it stronger
    • Can distribute the signal so as to influence several processes in parallel
  15. Hormones that can pass the plasma membrane
    • Small hydrophobic hormones
    • E.g. steroids
    • Bind to receptor proteins located either in the cytosol or the nucleus
    • These hormone receptors are proteins capable of regulating gene transcription, but they are typically present in an inactive form in unstimulated cells
    • When the receptor of a hormone binds, the receptor protein undergoes a large conformational change that activates the protein, allowing it to promote or inhibit the transcription of selected genes
  16. Which hormones cannot pass the plasma membrane?
    Large hydrophilic hormones
  17. Nitrous Oxide
    • NO is a gas that is able to cross the plasma membrane without a receptor
    • Made from arginine
    • Triggers smooth muscle relaxation (vasodilation)
    • Gives you boners
  18. NO's action
    • Binds to guanylyl cyclase, which stimulates the formation of cyclic GMP from the nucleotide GTP
    • Cyclic GMP is the next signaling molecule in the chain, which leads to cell response
    • Local blood-vessel dilation occurs
  19. Viagra
    Blocks the enzyme that degrades cyclic GMP, so the NO signal is maintained
  20. Cell surface receptors
    Use intracellular signaling pathways
  21. Intracellular signaling pathways
    • Relay signal onwar, spreading it
    • Amplify the signal, so few have a great affect
    • Receive other signals from other pathways
    • Distribute signal to other pathways
  22. Molecular switches
    • Signal switches from ative to inactive
    • Active - can turn on other proteins
    • Stay active until a signal turns them off
    • If a signaling pathway is to recover after transmitting a signal and make itself ready to transmit another, every molecular switch must be reset to its original, unstimulated state
  23. Two classes of molecular switches
    • Activated or deactivated by phosphorylation
    • GTP-binding proteins
  24. Activated or deactivation of molecular switches by phosphorylation
    • Protein kinase (adds phosphate)
    • Protein phosphatase (removes phosphate)
  25. GTP-binding proteins
    • Switch between active or inactive form depending on if GTP (active) or GDP (inactive) is bound
    • They can hydrolyze GTP on their own as they have GTPase activity
  26. Ion-channel-coupled receptors
    Open ion channels, and produce an electrical current
  27. G-protein coupled receptors
    Active GTP-binding proteins either activate an enzyme or ion channel
  28. Enzyme-coupled receptors
    • Act as enzymes or work with enzymes inside the cell
    • Switching on this enzymatic activitythen generates a hose of additional signals, including small molecules that are released into the cytosol
  29. Modification of cell-surface receptors
    • Natural ligand that is bound to the receptor can be mimicked by other molecules
    • These molecules can either bind to the ligand binding site or to another area on the receptor
    • This will either result in over-stimulation or blocking the receptors activity
  30. Nicotene
    Acts on neurotransmitter receptor in CNS and muscle cells which are also acted upon by acetylcholine
  31. G-protein-coupled receptors (GPCR)
    • Largest family of cell surface receptors
    • Target for drug development (more than half of drugs work on GPCRs)
  32. Olfactor receptor proteins (OR)
    • G-protein-coupled receptor
    • Largest gene family known in mammals
    • humans have 2-4 OR per cm2
    • dogs have 20-200 OR receptors per cm2
  33. G-protein-coupled receptors (GPCR)
    • Single protein chain
    • Weaves back and forth between PM
    • G protein located on underside of cell membrane, made of 3 units
    • Alpha, beta, and y components
  34. Cholera toxin
    • Binds to alpha subunit, and prevents GTPase activity, therefore it stays activated longer than it should
    • Causes prolonged release of Cl- and H2O
    • Can lead to deathly diarrhea and dehydration
  35. G proteins regulating ioin channels
    • Heartbeat regulated by 2 sets of nerves (1 speeds 1 slows)
    • Nerves that signal slowing of hear release acetylcholine
    • By complex open the K+ channels
    • K+ flows out and inhibits heart cells excitability
  36. Adenylyl cyclase
    • most common target enzyme for G-proteins
    • involved in making cyclic AMP
    • Activated Adenylyl cyclase catalyzes the syntehsis of cyclic AMP from ATP
    • Cyclic AMP activates cyclic AMP-dependent protein kinase (PKA)
    • Activated PKA catalyzes phosphorylation of serines or proteins
    • E.g. Adrenaline signal - ultimately causes the breakdown of glycogen in skeletal muscles
  37. Phospholipase C
    • Most common target enzyme for G protein
    • Inositol triphosphate and diacylglycerol
  38. Inositol phospholipid pathway
    • Inositol phospholipid (sugar)
    • Activated phospholipase C removes the sugar-phosphate head it creates 2 signaling molecules: inositol 1,4,5 -triphosphate (IP3) and diacylglycerol (DAG)
    • IP3 remains in cytosol
    • DAG remains in plasma membrain
    • IP3 opens Ca++ channels of ER and Ca++ increases in cytosol
  39. Calmodulin
    • Increases cytosolic Ca++ proteins
    • Activated Ca++ proteins have a conformation change and wrap around other proteins
  40. Rhodopsin
    • G-protein-coupled light receptor that controls non-color vision in mammals
    • Activates the G protein transducin which activates the intracellular signaling cascade which causes cation channels to close in photoreceptor cells
    • When light is dim, amplification of the signal is sent
    • When light is abundant, the signal cascade adapts and reduces the amplification so that the photoreceptor cells are not overwhelmed
  41. Cytoskeleton proteins
    • Intermediate filaments
    • Microtubules
    • Actin filaments
  42. Cytoskeleton
    • Intricate network of protein filaments that extends throughout the cytoplasm
    • Helps support the large volume of cytoplasm in eucaryotic cells
    • Directly responsible for large-scale movements such as the crawling of cells along a surface, contraction of muscle cells, and the changes in cell shape that take place as an embryo develops
    • Without cytoskeleton, wounds would never heal, muscles would be useless, and sperm would never reach the eggs
  43. Intermediate filaments
    • Maintain mechanical stress (most durable of proteins)
    • Surround the nucleus, and make a network throughout
    • Anchored to plasma membrane by desmosomes
    • Have a rope-like structure through noncovalent bonds
  44. Structure of intermediate filaments
    • rope-like structure through noncovalent bonds
    • Alongated fibrous proteins, each composed of N-terminal globular head, and C-terminal globular tail, and a central elongated rod domain
    • Rod domain consists of an extended alpha-helical region that enables pairs of intermediate filament proteins to form stable dimers by wrapping around each other in a coiled-coil fashion
    • Two of these coiled-coils then associate by noncovalent bonding to form a tetramer, and the tetramers then bind to one another end-to-end and side-by-side, also by noncovalent bonding, to generate the final ropelike intermediate filament
  45. Location of intermediate filaments
    • Muscle, nerve axons, epithelial
    • Prevent cells from breaking
  46. Classes of intermediate filaments
    • Keratins (epithelia)
    • vimentin and vimentin-related (connective tissue, muscle)
    • neurofilaments (nerve cells)
    • Nuclear lamins (strengthen the nuclear lamins of animal cells) - break down during cell division by phosphorylation/dephosphorylation
  47. Progeria
    • Loss of nuclear lamins leads to nuclear instability, which leads to impaired cell division and tissue repair
    • When young children age too quickly
  48. Microtubules
    • Long, relatively stiff hollow tubes responsible for anchoring membrane-enclosed organelles
    • Guide intracellular transport
    • Disassemble and reassemble
    • Form structures such as cilia and flagella
    • Work with motor proteins in order to move organelles
  49. Controsome
    • Small nuclear structure at the middle of the cell from which microfilaments grow
    • microtubules create a system of tracks within the cell, along which vesicles, organelles, and other cell components are moved
    • When a cell enters mitosis, the cytoplasmic microtubules disassemble and then reassemble into an intricate structure called the mitotic spindle
    • Provides the machinery that will segregate the chromosomes equally into two daughter cells just before a cell divides
  50. Composition of microtubules
    • Made up of alpha-tubulin and beta-tubulin bound by noncovalent bonding
    • Tubulin dimers are stacked linearly to make protofilaments (these protofilaments have polarity - positive and negative end)
    • Beta-tubulin end is the plus end (where growth occurs)
    • Alpha-tubulin end is the minus end
  51. What is the importance of a y-tubulin ring in centromeres
    allow for a specific site of orientation to allow new microtubules to grow
  52. Dynamic instability
    • Microtubules undergo a transition (GTP hydrolysis) and rapidly shorten, and possibly stop and elongate again
    • May shorten all the way, allowing y-tubulin ring to create a new microtubule
  53. What controls the growth of microtubules from a centrosome?
    • GTP hydrolysis
    • Growing microtubule will not be disassembled if it is stabilized by being attached to another structure
    • Capping proteins will stabilize the microtubule
  54. Antimitotic drugs
    Prevent the microtubules from polymerizing, and stops mitosis, which will kill the cells (used in cancer treatment)
  55. Saltatory movement
    • Directional intracellular movement (uses hydrolysis of ATP)
    • Generated by motor proteins, which bind to actin filaments or microtubules and use the energy derived from repeated cycles of ATP hydrolysis to travel steadily along the actin filament or the microtubule in a single direction
  56. Name the two types of motor proteins in microtubules
    • Kinesins (move toward the plus ends of the microtubules)
    • Dyneins (move towards the minus ends of the microtubules)
  57. Kinesins
    Attached to the outside of the ER membrane and pull it outward along microtubules, stretching it like a net
  58. Dyneins
    • Pull the golgi apparatus the other way along microtubules, inward toward the cell center
    • Help move cilia and flagella (have a 9+2 microtubule arrangement)
  59. Basal body
    Organizing center for the cilium
  60. Actins
    • Filaments are thin and flexible
    • Usually shorter than microtubules
    • usually cross-linked networks
    • Very involved with cell surface movements (microvilli, contractile ring in cell division)
    • Thymosin and prolifin regulate actin polymerization
  61. M phase
    • nucleus divides (mitosis) and cell splits in two (cytokinesis)
    • Ensures chromosomes are attached to mitotic spindle
  62. Interphase
    • The period between one M phase and the next
    • Cell increases in size
    • Encompasses the remaining three cycles of the cell
  63. S phase
    • Synthesis
    • The cell replicates its nuclear DNA, an essential prerequisite for cell division
    • Contains G1 and G2 phases
  64. G1 (gap) phase
    • Interval between the completion of M phase and the beginning of S phase
    • Cell monitors the internal and external environments to ensure the conditions are suitable and preparations are complete before it commits itself to the major upheavals of S phase and mitosis
  65. G2 (gap) phase
    • The interval between the end of S phase and the beginning of M phase
    • Makes sure DNA is not damaged before going into mitosis
  66. Cell-cycle control system
    • Coordinates the stages of the cell cycle
    • Involves biochemical switches such as phosphorylation and dephosphorylation as well as kinases and phophatases
  67. Cell-cycle control system machinery
    • Manufactures the new components of the growing cell
    • Hauls the components into their correct places and partitions them appropriately when the cell divides in two
    • These ensure correct progression through the cell cycle by regulating the cell-cycle machinery
  68. Cyclin-dependent protein kinases (Cdks)
    • Activation of these complexes trigger various cell-cycle events, such as entry into S phase or M phase
    • Regulated by phosphorylation and dephosphorylation
    • Removal of inhibitory phosphate groups by the phosphatase is the final step that activates the M-Cdk complex at the end of interphase
  69. Ubiquitin
    • Causes degredation of cyclins, which inactivates Cdks
    • Getting rid of the cyclin turns Cdk into its inactive form helping to transition the cell into the next stage
    • Destruction of M cyclin inactivates M-Cdk, which will have the cell leave mitosis
  70. Cdk inhibitor protein
    block the assembly of the cyclin Cdk or the activity of the complexes
  71. G0
    • Some cells never divide, and remain in G0
    • Nerves, muscles
  72. Checkpoint proteins
    • In G1 and S prevent starting or completing the S phase
    • G2 protein checkpoint stops it form going to M phase
    • p53 is a very important cancer checkpoint protein
  73. More M phase
    • Biggest problem is to properly segregate the chromosomes
    • M-Cdk triggers the condensation of chromosomes
    • Condensins help make chromosomes condense
  74. Cohesins
    Keep sister chromatids together
  75. Mitosis is divided into 6 stages
    • Prophase
    • Prometaphase
    • Metaphase
    • Anaphase Telophase
    • Cytokinesis
  76. Prophase
    • Replicated chromosomes, each consisting of two closely associated sister chromatids, condense
    • Outside the nucleus, the mitotic spindle assembles between the two centrosomes, which have begun to move apart
  77. Prometaphase
    • Starts abruptly with the breakdown of the nuclear envelope
    • Chromosomes can now attach to spindle microtubules via their kinetochores and undergo active movement
  78. Metaphase
    • Chromosomes are aligned at the equator of the spindle, midway between the spindle poles
    • The paired kinetochore microtubules on each chromosome attach to opposite poles of the spindle
  79. Anaphase
    • The paired chromatids synchronously seperate to form two daughter chromosomes, and each is pulled slowly toward the spindle pole it is attached to
    • The kinetochore microtubules get shorter, and the spindle poles also move apart, both contributing to chromosome seperation
  80. Telophase
    • Two sets of daughter chromosomes arrive at the poles of the spindle
    • A new nuclear envelope reassembles around each set, completing the formation of two nuclei and marking the end of mitosis. The division of the cytoplasm begins with the assembly of the contractile ring
  81. Cytokinesis
    The cytoplasm is divided in two by a contractile ring of actin and myosin filaments, which pinches in the cell to create two daughters, each with one nucleas
  82. Programmed cell death
    Intracellular programming of killing off cells, the most common mechanism is apoptosis
  83. Caspase
    Family of proteases that are activated by signals which induce apoptosis
  84. Procaspase
    Active form of caspase, activate other members of family by cleaving each other, which amplifies their activity
  85. Bc12
    • Promote procaspase activation
    • Bax and Bak
    • Some Bc12 also inhibit activation of procaspase
  86. Bax and Bak
    • activate procaspases indirectly by inducing the relase of cytochrome cfrom mitochondria into the cytosol
    • Cytochrome c binds to an adaptor protein, which then activates a specific procaspase
    • Activated procaspase initiates the caspase cascade that leads to apoptosis
    • Bax and Bak proteins are themselves activated by other death-promoting members of the Bc12 family, which are produced or activated by various insults to the cell, such as DNA damage
  87. Survival factors
    • Promote cell survival by largely suppressing apoptosis
    • Usually bind to cell surface receptors
    • Keep death programming suppressed by regulating the Bc12 family of proteins
  88. Mitogens
    • Stimulate cell division, by overriding the molecular brakes that tend to block progression through the cell cycle
    • Bind to cell surface, which stimulates cell division
    • Mainly work by releasing the molecular brakes from G1 to S phase
  89. Growth factors
    • Promote the synthesis and inhibit degredation of proteins and other macromolecules
    • Bind to cell surface receptors which activate intracellular signaling pathways
    • Also help to ensure cells proper size as they replicate
  90. Nondisjunction
    • Homologs seperating imporperly
    • Results in improper number of chromosomes (trisomy 21)
    • Occurs in about 10% of human oocytes
    • Less often in males (they have a checkpoint mechanism)
Card Set
Cell Biology 2
Shit goes hard