Cell Biology Lecture 20
Cell Biology Lecture 20 BIOL 225
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This 5 page Class Notes was uploaded by MelLem on Thursday April 21, 2016. The Class Notes belongs to BIOL 225 at Simmons College taught by Dr. Lopilato in Fall 2016. Since its upload, it has received 12 views. For similar materials see Cell Biology in Biology at Simmons College.
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Date Created: 04/21/16
Cell Biology BIOL 225 Lecture 20 Chapter 14 – Cell Division Cell Division • Planarians (whole organism) and newts (limbs) are good examples of cell division. • C. Elegan (worm) only has 156 cells for its entire life and does not divide. • Epithelial cells are replaced in the body every 5 days. • Cell cycle • Types of Cells 1. Do not divide • In humans, neurons, muscle cells and red blood cells do not divide. 2. Can be induced to divide • Liver cells (donate, and then they grow to the proper size in both the organism that donated it and the organism that received it. • Lymphocytes – divide when there is an infection 3. High level of division • Skin cells, epithelial cells • Stem cells • Bone marrow • Mechanism – microtubules o Allows the cells to divide Cell Cycle • Two phases o Interphase (consists of subphases) ▯ G1-‐ metabolism, growth, division of organelles ▯ S Phase – DNA replication, chromosomes duplicate ▯ G2 Phase – preparation for mitosis o Mitosis – chromosome division and cell division What is MPF? • MPF – (Mitosis Promoting Factor) is maturation promoting factor and contains a kinase subunit and a regulatory subunit called cyclin. • Increased concentrations of cyclin activate MPF. • Levels of cyclin protein fluctuate during the cell cycle so that MPF is only active when the cell is ready for mitosis. • This is produced then immediately degraded. Kinase Activity is Essential for Cell Cycle Regulation 1. Cyclin Binds to cdc2 Kinase. CAK phosphorylates to amino acids. 2. Dephosphorylation of Try15 by the cdc25 phosphate. Active cdc2 Kinase cell drives cells into mitosis 3. Cyclin degradation and inactivation of cdc2Kinase b. • Add phosphate kinase – remove phosphate • Active MPF molecule = mitosis • Kinase is inactivated from phosphorylation • Controlling protein activity • Degradation –tag with ubiquitin and send to proteasome to be degraded to individual amino acids. Control of Cell Cycle • Checkpoint between G1, S G2, M • Entry into M phase – need MPF o Kinase + Cyclin = MPF o Inactive ▯▯ active state o Cyclin goes up and down (fluctuates) • Variations in level of active MPF • Role of MPF o Active MPF stimulates nuclear envelope breakdown. • CDK – Cyclin Dependent Kinases • Using different cyclins and CDKs to go through different check points. (See figure below) Stages of Mitosis • S Phase – chromosomes duplicated • Prophase – Chromosomes Condense • Metaphase – Line up with the spindle fibers. Each chromosome attached to spindle fiber • Anaphase – They separate from the metaphase plate • Telophase – Go to the poles of the cell. Kinetochore – Structures on the outer surface of the centromere that attach to the chromosomes. Centrosomes and the Formation of Spindle Fibers • Centrosomes contain a pair of centrioles. • Mitotic (MTOC) nucleating centers to add tubulin (alpha and beta) • In G1 – centrosome has 1 pair of centrioles. • Late in G1, they duplicate (The big centrioles are the “mothers” The small are the “daughters” • Centrioles generate microtubules that go to the poles. • A PAIR of centrioles = centrosome • MTOC’s can be centrosomes (of basal bodies in cilia and flagella) • You only want two centrosomes, the chromosomes don’t line up correctly when you have more than 2 centrosomes. Force Required for chromosome movement at anaphase • Microtubules on both the positive ends has depolymerization (so the fibers shorten) • Kinesis Mediated Depolymerization What happens if DNA damage can not be repaired? • Apoptosis – programmed cell death • Apoptosis is an ordered process involving cell shrinkage, loss of adhesion to other cells, dissection of chromatin and engulfment by phagocytosis. • DNase – Breaks down DNA • Apoptotic cells sent out signals to macrophages Clearance of Apoptotic cells is accompanied by Phagocytosis • Phosphatidyl serine – goes from inner leaflet by enzyme called “scramblase” (signals to macrophage) • Phosphatidyl Serine has a glycerol backbone o Fatty acids o Has phosphate group o Has a serine group after the phosphate group. Apoptosis • Apoptotic changes are actiated by proteolytic enzymes called caspases, which target: o Protein kinases, some of which cause detachment of cells. ▯ Focal Adhesion Kinase (PHK) – Cells lose adhesion properties to other cells. o Lamins, which line the nuclear membrane o Proteins of the cytoskeleton ▯ All get degraded o Caspase activated DNase (CAD) The extrinsic (Receptor-‐Mediated) Pathways of apoptosis • Sets off cleavage • Initiator Caspase – works on the executioner caspase • Leads to cell death • Active form is a result of cleavage • Protein Activation by: 3 ways o Caspases – cleavage o Phosphorylation – some may be active when they have phosphates or inactive when they have phosphates o Active GTP • Extrinsic Receptor o Stress Response to ionizing mediation o High temperature – like when we have a fever o Viral infections o Chemotherapy – the toxic chemicals. The intrinsic (mitochondria-‐mediated) pathway of apoptosis • Intrinsic – responds to DNA damage (hypoxia – low O2 • Takes less than 1 hour to kill cells. • Biel Proteins – some are apoptotic, some are antiapoptotic • Bax -‐ Cytochrome C is in intermembrane space • Bax and Bak both make channels in our membrane and release cytochrome C. • Cytochrome C is released in ~ minutes (really quick signal)
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