Molecular Cell Biology Chapter 21: Cells of the Nervous System

Molecular Cell Biology Chapter 21: Cells of the Nervous System

21.1: Overview of the Cell Cycle and Its Control

• Phases of the cell cycles:

• M (mitosis)
• G1 (between mitosis and DNA replication initiation
• S (DNA replication)
• G2 (between DNA replication completion and mitosis)

• Cyclin-CDK complexes regulate the progress of a cell through the cell cycle, and are made up of a regulatory cyclin subunit along with a cyclin dependent inase subunit
• Chromosomal condensation and the disassembly of G1 and G2 cells nuclear envelope is caused by dissusible cyclin CDK
• Yeast cell division isolation mutants help with identifying genes which help regulate the cell cycle
• Eggs and early embryos of amphibians and invertebrates when fertilized provide extract sources which help in biochemical studies for the cell cycles events

21.2: Biochemical Studies with Oocytes, Eggs and Early Embryos

• Mitotic cyclin activity is needed for protein kinase MPF
• MPF activity in the cells as they enter mitosis increases along witht the concentration of mitotic cyclins
• MPF activities rise and fall is resulted by concomitant synthesis and mitotic cycle degradation
• Ubiquitin ligase activity of the APC is controlled so the late anaphase is the only time that mitotic cyclins are polybiquitinated and not before

21.3: Genetic Studies with S. pombe

• The fission yeast S. pombe gets encoded a cyclin dependent protein kinase which is associated with a mitotic cyclin, which results in a mytotic cyclin CDK heterodimer
• Two residues in the catalytic CDK subunit being at a certain phosphorylation state effects protein kinase activity of the cyclin CDK complex
• Onset of mitosis is effected by an actuated mitotic cyclin CDK complex, which is dependent of a decrease of Wee1 and increase of Cdc25
• S. pombe MPF and human cyclin A-CDK2 complex are similar to eachother

21.4: Molecular Mechanisms for Regulating Mitotic Events

• MPF catalyzed phosphorylation of lamins A, B, and C along with inner nuclear proteins and nucleuporins occours early in mitosis
• Kinase regulates the phosphorylation of condensin complexes powered by MPF
• DNA replication in the S phase form sister chromatids that are linked at the centromere because of cohesion complexes
• Cdc20 directs APC to polybiquitinate securin at the onset of anaphase
• The APC polybiquitinates mitotic cyclins with the direction of Cdh1 after sister chromatids move to spindle pores
• Protein phosphates are able to remove regulatory phosphates such as:

• Condensin
• Lamins
• Nucleoporins

• They are able to do this when MPF activity falls
• MPF activity falling also helps with the removal of inhibition of myosin light chain, which lets the cleavage furrow form into cytokenisis

21.5: Genetic Studies with S. cerevisiae

• The single cyclin dependent kinase (CDK) which is encoded by CDC28 is expressed by S. cerevisiae
• The three cyclins active in G1:

• Cln1
• Cln2
• Cln3

• Heterodimers are formed with CDK when Clb3 and Clb4 are expressed during the S phase
• DNA replication takes place at certain origins only once until a cell goes through anaphase

21.6: Cell Cycle Control in Mammilian Cells

• Mitogens which are peptide growth factors make mammalian cells that are cultured proliferate
• This helps guide cells into the S phase, G2 phase and mitosis even without growth factors present
• Mammilan cells regulation requires CDKs and cyclins
• Cyclin CDK conmplexes are regulated phosphorylation and dephosphorylation in mamaillian cells

21.7: Checkpoints in Cell Cycle Regulation

• The endurance that chromosomes are intact in cells and that the cell cycle is progressing properly is given by checkpoint controls
• Unreplicated DNA checkpoint

• During S and G1
• Prevent MPF before the synthesization of DNA
• Activates CDK1 and Cdc25c

• Spindle assembly checkpoint:

• Prevents premature anaphase
• Uses Mad2 and other proteins for the regulation of APC

• Chromosome segregation checkpoint

• Makes sure telophase and cytokenisis occur after daughter cells have been segregated
• Allows for daughter cells to have a full set of chromosomes

• DNA damage checkpoint

• Arrests cell until DNA damage is fixed if any DNA damage occurs
• Three tumor suppressor proteins are needed here:

• ATM/ATR
• Chk1
• p53

21.8: Meiosis: A Special Type of Cell Division

• One cycle of chromosome replication and two cycles of cell division are needed in meiosis for the production of haploid germ cells
• Chromatids and homologous chromosomes have at least one recombination occur between them
• Cell cycle proteins that work in mitotically dividing cells also work in meiosis undergoing cells