The Nucleus. Definition Structure Ultrastructure Molecular organization of nuclear components. Definition
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1 The Nucleus Definition Structure Ultrastructure Molecular organization of nuclear components Definition The largest organelle Membrane-bounded (nuclear envelope) Contains most of the cell s DNA Role: protection of genetic information, assuring its transmission, and further its use ALL SOMATIC CELLS OF ONE ORGANISM HAVE THE SAME GENES 1
2 Nucleus structure LM staining characteristics Heterochromatic nuclei Endothelial nuclei Dr. Mircea Leabu - The Cell Nucleus (lecture iconography) Euchromatic nuclei Nuclei with obvious nucleoli Neurons Nucleus structure LM - Number The rule: one cell one nucleus Transitional epithelium in urinary bladder HE 40x Liver Best Staining 80x 2
3 Nucleus structure LM - Number Anucleated cells Erythrocytes Stratified squamous epithelium Nucleus structure LM morphology Gastric glands cross section HE 40x 3
4 Nucleus structure LM morphology Intestinal villus HE 60x content/ uploads/2009/04/leukocytes.jpg Nucleus ultrastructure 4
5 Dr. Mircea Leabu - The Cell Nucleus (lecture iconography) Nucleus ultrastructure Nucleus ultrastructure Nuclear envelope dephosphorylated lamins A, B and C 5
6 Nucleus ultrastructure Nucleus organization Chromatin organization Transcription Nucleolus Nuclear envelope 6
7 Chromatin organization 24 DNA molecules (50x x10 6 bp) 24 chromosomes (22 autosome, 2 sex) 2x3x10 9 bp in human DNA 1,7 8,5 cm/molecule Chromatin a complex of DNA with histones and non-histonic chromosomal proteins Histones highly positive proteins (lysine and arginine): Nucleosomal histones (H2A, H2B, H3, H4) aa Histone H1 (6 subtypes) 220 aa (linker histone) Nucleosome the structural unit of chromatin 7
8 Nucleosome packing Chromatin folding levels 8
9 Chromosome sequences Human chromosomes 9
10 RNA synthesis Transcription 3 types of RNA polymerases (I, II, III) mrna synthesis RNA polymerase II rrna synthesis RNA polymerase I (28S, 18S, 5,8S) RNA polymerase III (5S) trna synthesis RNA polymerase III Dr. Mircea Leabu - The Cell Nucleus (lecture iconography) RNA biosynthesis 10
11 Nucleolus ultrastructure Nucleolus function 11
12 The nuclear envelope Endomembrane bound structure External membrane; attached polyribosomes Internal membrane; attached nuclear lamina Lumen; anastomosed with ER lumen Nuclear pores Role: DNA hostage, protection and usage (chromatin) Control of nucleus - cytosol transport events Nuclear lamina A fibrillar network organized by proteins belonging to intermediate filament category lamins (60-80kDa) Three classes of lamins: A, B and C Attached to internal face of the inner membrane of the nuclear envelope 12 Functions of the nuclear lamina: - chromatin organization and DNA replication - nuclear envelope organization control (interphase versus mitosis): -lamins phosphorylation = disorganization - lamins dephosphorylation = reorganization - defects in nuclear lamina organization diseases = laminopaties (genetic disorders): - Emery-Dreifuss muscular dystrophy - a muscle wasting disease - Progeria - premature aging - Restrictive dermopathy - a disease inducing extremely tight skin and other severe neonatal abnormalities
13 Nucleus to cytoplasm transport Nuclear pore complex nucleoporins (Nup) ~ 30 types of Nup The nuclear pore complex - octagonal symmetry - >450 protein molecules - several structural subunits - Mr >120 millions of Da - central channel ~9nm - total diameter ~120nm 13
14 Protein import into nucleus Mr below 40kDa Mr higher than 40kDa Signal peptide Factors assuring/controlling transport through nuclear pores Signal peptide nuclear localization signals (NLS) or nuclear export signals (NES) Karyopherins importins or exportins Small GTP-ases (Ran GTP-ases; Ran from Rasrelated nuclear protein) Pathological implications: several malignancies (myeloid leukemia, other cancers) viral infections (i.e. DNA viruses) some autoimune diseases (systemic lupus erythematosus, rheumatoid arthritis and primary biliary cirrhosis) 14
15 Cytoplasm to nucleus transport active transport Summary on nucleus Is the compartment for genetic information protection, usage, conserving and transmission Contains all necessary enzymes for replication and transcription of genetic information Prepares essential components for genetic information translation (ribosomal subunits, mrna) Nucleus function needs a permanent exchange of substance and information with the cytoplasm These exchanges are assured by the specific structure of nuclear envelope, allowing under a rigorous control a transport from nucleus to the cytosol (in both directions), through the nuclear pores There are pathologies related to the right organization and function of the nuclear elements 15
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