Nucleus and Nucleolus PDF

NUCLEUS and NUCLEOLUS A.Banu DEMİR 06.11.2024 Learning Objectives 1. Describe the structure of nucleus 2. List the general functions of nucleus and nuclear structures 3. Explain how certain proteins are transported through nuclear membrane  THE NUCLEUS the principle feat...

NUCLEUS and NUCLEOLUS A.Banu DEMİR 06.11.2024 Learning Objectives 1. Describe the structure of nucleus 2. List the general functions of nucleus and nuclear structures 3. Explain how certain proteins are transported through nuclear membrane  THE NUCLEUS the principle feature that distinguishes eukaryotic cells from prokaryotic cells stores genetic information and acts as cell’s control center provides limited access of proteins to the genetic material.  THE STRUCTURE OF NUCLEUS Major Components: the double nuclear membrane a fibrous meshwork that provides structural support Nuclear envelope to the nucleus. Nuclear lamina site within the nucleus, where ribosomal Nucleolus (Nucleoli in plural) RNA (rRNA) is synthesized and begins to Nucleoplasm assemble into ribosomes Chromatin the milieu in which other intra- nuclear components are a complex of DNA and embedded. It consists of proteins that forms enzymatic and non-enzymatic chromosomes within proteins, metabolites, ions, and the nucleus of water. eukaryotic cells.  THE STRUCTURE OF NUCLEUS Major Components: Nuclear envelope Nuclear lamina Nucleolus (Nucleoli in plural) Nucleoplasm Chromatin  Structure of the Nuclear Envelope consist of; two membranes (outer and inner membranes) an underlying nuclear lamina nuclear pore complexes (NPCs) Transport of molecules through nuclear envelope occurs through nuclear pore complexes. Each nuclear membrane is a phospholipid bilayer permeable only to small nonpolar molecules  The outer nuclear membrane is continuous with the endoplasmic reticulum, functionally similar to the membranes of the E.R. has ribosomes bound to its cytoplasmic surface the inner nuclear membrane carries proteins that are specific to the nucleus, such as those that bind the nuclear lamina  Function of the Nuclear Envelope critical function is to act as a barrier that separates the contents of the nucleus from the cytoplasm maintain the nucleus as a distinct biochemical compartment. the only channels through the nuclear envelope (nuclear pore complexes) allow the regulated exchange of molecules between the nucleus and the cytoplasm  The Structure of Nuclear Pore Complex The nuclear envelope contains holes where the inner and outer membranes fuse together to create pores  a basket-like structure  The Function of Nuclear Pore Complex allow communication between the Nucleus and Cytosol responsible for the selective traffic of proteins and RNAs between the nucleus and the cytoplasm. rRNA, transfer RNA (tRNA), and messenger RNA (mRNA) made in the nucleus must be exported to the cytoplasm, and proteins made in the cytoplasm must be imported into the nucleus. This bidirectional transport occurs through the nuclear pores Import And Export Through The Nuclear Pore Complex proteins imported from the cytoplasm to the nucleus include histones, DNA polymerases, RNA poly- merases, transcription factors, splicing factors, etc. These proteins are targeted to the nucleus by specific amino acid sequences called nuclear localization signals (NLS). The selective transport of material into the nucleus occurs only when energy-generating molecules (guanosine triphosphate [GTP]) are present. Nuclear Localization Signals Alan Smith : identification of a short amino acid sequence that serves a nuclear localization signal most RNAs are exported from the nucleus to the cytoplasm. Since proteins are synthesized in the cytoplasm, the export of mRNAs, rRNAs, and tRNAs is a critical step in gene expression in eukaryotic cells. The export from the nucleus requires nuclear export signals (NES). Import And Export Through The Nuclear Pore Complex 2 types of proteins play critical roles in protein transport through the nuclear pore complex: 1. nuclear transport receptors (karyopherins) importin: transport macromolecules from cytoplasm into the nucleus exportin: export macromolecules from nucleus to the cytoplasm 2. small GTP binding protein called Ran Visualizing active import through NPCs Nuclear import receptors(importins) Nuclear export receptors (exportins) https://www.youtube.com/watch?v=ZGPpKk-6-K0 4 min Import And Export Through The Nuclear Pore Complex Importin-Ran/GDP Exportin-Ran/GTP  Example: The control of nuclear import during T cell activation When T cells are activated by In high Ca2+,the protein phosphatase calcineurin binds to NF-AT and foreign antigen, the intracellular dephosphorylates it  exposes nuclear import signals and blocks a Ca2+ concentration increases. nuclear export signal NF-AT and calcineurin complex is imported into the nucleus NF-AT activates the transcription of numerous The nuclear factor of genes required for T cell activation. activated T cells (NF-AT) is a transcription regulatory protein that, in the resting T cell, is found in the cytosol in a phosphorylated state. Rephosphorylation of NF-AT inactivates the The response shuts off when Ca2+ levels nuclear import signals and re-exposes the decrease, releasing NF-AT from nuclear export signal, causing NF-AT to calcineurin. relocate to the cytosol. Some of the most potent immunosuppressive drugs, including cyclosporin A and FK506, inhibit the ability of calcineurin to dephosphorylate NF- AT and thereby block the nuclear accumulation of NF-AT and T cell activation.  Example: Feedback regulation of cholesterol biosynthesis SREBP(sterol response Low cholesterol element binding protein), concentrations cholesterol a latent transcription regulator that controls expression of binding site on SCAP is empty cholesterol biosynthetic  SCAP changes conformation enzymes, is initially and is packaged together with synthesized as an ER SREBP into transport membrane protein. vesicles which deliver their Sufficient cholesterol cargo to the Golgi anchored in ER membrane by apparatus,where two Golgi- interaction with another ER resident proteases cleave membrane protein, called SREBP to free its cytosolic SCAP(SREBP cleavage activation protein), which binds domain from the membrane. cholesterol. The cytosolic domain then moves into the nucleus, where it binds to the promoters of genes that encode proteins involved in cholesterol biosynthesis and activates their transcription. In this way, more cholesterol is made when its concentration falls below a threshold.  THE STRUCTURE OF NUCLEUS Major Components: Nuclear envelope Nuclear lamina Nucleolus (Nucleoli in plural) Nucleoplasm Chromatin The Structure of Nuclear Lamina The inner nuclear membrane contacts an underlying nuclear lamina, a network made from fibrous proteins called lamins. a class of intermediate filament proteins  Like other intermediate filament proteins, the lamins associate with each other to form higher order structures. Mammalian cells have three lamin genes; A, B, and C; which code for at least seven distinct proteins. The Functions of the Nuclear Lamina provides the structural support to the nucleus the lamins bind to specific inner nuclear membrane proteins such as emerin and the lamin B receptor, mediating their attachment to the nuclear envelope and localizing the nuclear lamina also binds to chromatin through histones H2A and H2B as well as other chromatin proteins Many nuclear proteins that function in DNA synthesis, transcription, or chromatin modification are known to bind lamins.  Nuclear Lamina Diseases X-linked Emery-Dreifuss muscular dystrophy (mutations in a novel transmembrane protein emerin localized to the inner nuclear membrane leads absence of this protein in patients) Non-sex- linked Emery-Dreifuss muscular dystrophy (mutations in LMNA, the single gene encoding nuclear lamins A and C). Different mutations in the LMNA gene ; Dunnigan-type partial lipodystrophy Charcot-Marie-Tooth disorder type 2Bl a disease that causes premature ageing- Hutchinson-Gilford progeria syndrome  THE STRUCTURE OF NUCLEUS Major Components: Nuclear envelope Nuclear lamina Nucleolus (Nucleoli in plural) Nucleoplasm Chromatin  Sub-compartments within Nucleus localization of most nuclear processes to distinct regions of the nucleus The nuclei of mammalian cells contain clustered sites of DNA replication within which the replication of multiple DNA molecules takes place.  PML bodies are known to interact with chromatin and are the sites of accumulation of transcription factors and chromatin-modifying proteins Cajal bodies contain the characteristic protein coilin and are enriched in small RNPs. They are believed to function as sites of Ribonucleoprotein (RNP) assembly, especially in the final steps of snRNP processing. The Nucleolus and Ribosomal RNA (rRNA) Processing The most prominent nuclear body is the nucleolus: the site where ribosomal RNA (rRNA) is synthesized and begins to assemble into ribosomes. Cells require large number of ribosomes at specific times to meet their needs for protein synthesis Actively growing mammalian cells, for example, contain 5 million to 10 million ribosomes that must be synthesized each time the cell divides. The nucleolus is a ribosome production factory, designed to fulfill the need for regulated and efficient production of rRNAs and assembly of the ribosomal subunits. size and shape of the nucleolus is dependent on its activity. In cells that are actively synthesizing large amounts of proteins, may occupy up to 25% of the total nuclear volume, whereas in dormant cells, it may be hardly visible. The size and shape or number of visible nucleolar centers in the nucleus can be used in pathologic examinations as a determinant of the particular cell.  THE STRUCTURE OF NUCLEUS Major Components: Nuclear envelope Nuclear lamina Nucleolus (Nucleoli in plural) Nucleoplasm Chromatin  the milieu in which other intra-nuclear components Nucleoplasm are embedded. It consists of enzymatic and non- enzymatic proteins, metabolites, ions, and water.  THE FUNCTION OF NUCLEUS 1. It controls the activities of the cell by determining which protein molecules are produced by the cell and when they are produced. (e.g. It initiates and controls cell division in the organism) 2. It stores most of the cell’s genetic information. 3. rRNAs that code for the ribosomal subunits, are synthesized in the nucleolus of the nucleus. 4. The synthesis of DNA (replication) and RNA (transcription) occur in the nucleus  WRAP UP 1) Describe the structure of the nucleus Nuclear envelope; nuclear lamina, nuclear pore complexes, Nucleoplasm, Nucleolus 2) List the general functions of the nucleus and nuclear structure controls the activities of the cell stores most of the cell’s genetic information initiates and controls cell division in the organism Nuclear Envelope: act as a barrier that separates the contents of the nucleus from the cytoplasm , maintain the nucleus as a distinct biochemical compartment. Nuclear lamina: provides the structural support to the nucleus Nuclear pore complexes:allow communication between the nucleus and cytosol Nucleoplasm: contains the cell’s DNA Nucleolus: the site where ribosomal RNA (rRNA) is synthesized and begins to assemble into ribosomes  WRAP UP 3) Explain how certain proteins are transported through nuclear membrane the selective traffic of proteins and RNAs between the nucleus and the cytoplasm occur through nuclear pore complexes Nuclear transport receptors (importin and exportin) play role in transport Nuclear localization signal is required for protein import into the nucleus and nuclear export signal is required for protein export from the nucleus.