Cell Biology 2

• 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

Rhodopsin activates G protein transducin which activates intracellular cascade of ion channels to close photoreceptor cells

• Contact causes phosphorylation of other tail
• Phosphorylation causes signaling proteins to be activated
• Protein tyrosine phosphatase removes phosphates (terminates the signal)

• Dimeric transmembrane proteins
• Empty receptor is active (activates a protein kinase which shuts off ethylene-responsive genes

Send a general communication throughout the body and are produced by endocrine cells

Message converted from one form to another

• 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

• 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

Junctions where electrical signals are converted into chemical signal (neurotransmitter) which diffuses across the gap

• 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

Most animal cells are programmed to kill themselves

• Also known as a receptor
• Activated by only one type of signal

• Receptor receives an external signal and generates a new intracellular signal in response
• The internal signal is passed on until a response is generated

• 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

• 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

Large hydrophilic hormones

• 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

• 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

Blocks the enzyme that degrades cyclic GMP, so the NO signal is maintained

Use 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

• 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

• Activated or deactivated by phosphorylation
• GTP-binding proteins

• Protein kinase (adds phosphate)
• Protein phosphatase (removes phosphate)

• 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

Open ion channels, and produce an electrical current

Active GTP-binding proteins either activate an enzyme or ion channel

• 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

• 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

Acts on neurotransmitter receptor in CNS and muscle cells which are also acted upon by acetylcholine

• Largest family of cell surface receptors
• Target for drug development (more than half of drugs work on GPCRs)

• 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

• 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

• 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

• 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

• 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

• Most common target enzyme for G protein
• Inositol triphosphate and diacylglycerol

• 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

• Increases cytosolic Ca++ proteins
• Activated Ca++ proteins have a conformation change and wrap around other proteins

• 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

• Intermediate filaments
• Microtubules
• Actin filaments

• 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

• 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

• 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

• Muscle, nerve axons, epithelial
• Prevent cells from breaking

• 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

• Loss of nuclear lamins leads to nuclear instability, which leads to impaired cell division and tissue repair
• When young children age too quickly

• 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

• 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

• 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

allow for a specific site of orientation to allow new microtubules to grow

• 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

• GTP hydrolysis
• Growing microtubule will not be disassembled if it is stabilized by being attached to another structure
• Capping proteins will stabilize the microtubule

Prevent the microtubules from polymerizing, and stops mitosis, which will kill the cells (used in cancer treatment)

• 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

• Kinesins (move toward the plus ends of the microtubules)
• Dyneins (move towards the minus ends of the microtubules)

Attached to the outside of the ER membrane and pull it outward along microtubules, stretching it like a net

• 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)

Organizing center for the cilium

• 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

• nucleus divides (mitosis) and cell splits in two (cytokinesis)
• Ensures chromosomes are attached to mitotic spindle

• The period between one M phase and the next
• Cell increases in size
• Encompasses the remaining three cycles of the cell

• Synthesis
• The cell replicates its nuclear DNA, an essential prerequisite for cell division
• Contains G1 and G2 phases

• 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

• The interval between the end of S phase and the beginning of M phase
• Makes sure DNA is not damaged before going into mitosis

• Coordinates the stages of the cell cycle
• Involves biochemical switches such as phosphorylation and dephosphorylation as well as kinases and phophatases

• 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

• 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

• 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

block the assembly of the cyclin Cdk or the activity of the complexes

• Some cells never divide, and remain in G0
• Nerves, muscles

• 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

• Biggest problem is to properly segregate the chromosomes
• M-Cdk triggers the condensation of chromosomes
• Condensins help make chromosomes condense

Keep sister chromatids together

• Prophase
• Prometaphase
• Metaphase
• Anaphase Telophase
• Cytokinesis

• 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

• Starts abruptly with the breakdown of the nuclear envelope
• Chromosomes can now attach to spindle microtubules via their kinetochores and undergo active movement

• 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

• 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

• 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

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

Intracellular programming of killing off cells, the most common mechanism is apoptosis

Family of proteases that are activated by signals which induce apoptosis

Active form of caspase, activate other members of family by cleaving each other, which amplifies their activity

• Promote procaspase activation
• Bax and Bak
• Some Bc12 also inhibit activation of procaspase

• 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

• Promote cell survival by largely suppressing apoptosis
• Usually bind to cell surface receptors
• Keep death programming suppressed by regulating the Bc12 family of proteins

• 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

• 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

• 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)