Chapter 1: The Cell as a Unit of Health and Disease Flashcards
Five major classes of functional non-protein-coding sequences in the human genome AND their function?
- Promoter and enhancer regions that provide binding sites for transcription factors.
- Binding sites for factors that organize and maintain higher order chromatin structures.
- Noncoding regulatory RNAs. Over 60% of the genome is transcribed into RNAs that are never translated but regulate gene expression through a variety of mechanisms. The two best-studied varieties—micro-RNAs (miRNAs) and long noncoding RNAs (lncRNAs)—are described later.
- Mobile genetic elements (e.g., transposons) make up more than a third of the human genome. These “jumping genes” can move around the genome during evolution, resulting in variable copy number and positioning even among closely related species (e.g., humans and other primates). Although implicated in gene regulation and chromatin organization, the function of mobile genetic elements is not well established.
- Special structural regions of DNA, in particular, telomeres (chromosome ends) and centromeres (chromosome “tethers”). A major component of centromeres is so-called satellite DNA, consisting of large arrays—up to megabases in length—of repeating sequences (from 5?bp up to 5?kb). Although classically associated with spindle apparatus attachment, satellite DNA is also important in maintaining the dense, tightly packed organization of heterochromatin (discussed later).
The two most common forms of DNA variation in the human genome?
- SNPs
- CNVs
Histone marks and their effect(s) on transcription?
- Histone methylation. Both lysines and arginines can be methylated by specific writer enzymes; methylation of histone lysine residues can lead to transcriptional activation or repression, depending on which histone residue is marked.
- Histone acetylation. Lysine residues are acetylated by histone acetyltransferases (HATs), whose modifications tend to open the chromatin and increase transcription. In turn, these changes can be reversed by histone deacetylases (HDACs), leading to chromatin condensation.
- Histone phosphorylation. Serine residues can be modified by phosphorylation; depending on the specific residue, the DNA may be opened for transcription or condensed and inactive.
- DNA methylation. High levels of DNA methylation in gene regulatory elements typically result in transcriptional silencing. Like histone modifications, DNA methylation is tightly regulated by methyltransferases, demethylating enzymes, and methylated-DNA-binding proteins.
- Chromatin organizing factors. Much less is known about these proteins, which are believed to bind to noncoding regions and control long-range looping of DNA, thus regulating the spatial relationships between enhancers and promoters that control gene expression.
Role of cytosol (1)
- Metabolism
- Transport
- Protein translation
Role of mitochondria (1)
- Energy generation
- Apoptosis
Role of rough ER (1)
Synthesis of membrane and transport proteins
Role of smooth ER, Golgi (1)
- Protein modification
- Sorting
- Catabolism
Role of nucleus (1)
- Cell regulation
- Proliferation
- DNA transcription
Role of endosomes (1)
Intracellular transport and export
Role of lysosomes (1)
Cellular catabolism
Role of peroxisomes (1)
Very long-chain fatty acid metabolism
Specific phospholipids that interact with particular membrane proteins and modify their distributions and functions?
- Phosphatidylinositol
- Phosphatidylserine
- Glycolipids
- Sphingomyelin
The plasma membrane is liberally studded with a variety of proteins and glycoproteins involved in..?
- Ion and metabolite transport
- Fluid-phase and receptor-mediated uptake of macromolecules
- Cell-ligand, cell-matrix, and cell-cell interactions
Name different types of transmembrane transport.
- Carrier
- Channel
- Endocytosis (caveolae- and receptor-mediated)
- Exocytosis
- Phagocytosis
- Transcytosis
3 major classes of cytoskeletal proteins?
- Actin microfilaments
- Intermediate filaments
- Microtubules
Function(s) of intermediate filaments?
Provide tensile strength so that cells can bear mechanical stress
Function(s) of actin microfilaments?
- Control cell shape and movement
- Vesicular transport (with myosin)
- Epithelial barrier regulation (with myosin)
- Cell migration (with myosin)
Function(s) of microtubules?
- Serve as mooring lines for molecular motor proteins that use ATP to translocate vesicles, organelles, or other molecules around cells. There are two varieties of these motor proteins, kinesins and dyneins, that typically (but not exclusively) transport cargo in anterograde (− to +) or retrograde (+ to −) directions, respectively.
- Mediate sister chromatid segregation during mitosis.
- Form the core of primary cilia, single nonmotile projections on many nucleated cells that contribute to the regulation of cellular proliferation and differentiation
- Can be adapted to form the core of motile cilia (e.g., in bronchial epithelium) or flagella (in sperm).
Cell-cell junctions are organized into which basic types?
- Occluding junctions (tight junctions)
- Anchoring junctions (adherens junctions and desmosomes)
- Communicating junctions (gap junctions)
Function(s) of occluding junctions?
- Forming a selectively permeable barrier that seals the space between cells
- Represents the boundary that separates apical and basolateral membrane domains and helps to maintain cellular polarity
Function(s) of anchoring junctions?
Mechanically attach cells—and their cytoskeletons—to other cells or the ECM
Function(s) of communicating junctions?
Play a critical role in cell-cell communication
3 main mitochondrial functions?
- Energy/ATP generation: oxidative phosphorylation
- Intermediate metabolism: anaerobic glycolysis
- Cell death (necrosis and apoptosis)
Name intermediate filaments and their cell types.
- Vimentin, in mesenchymal cells (fibroblasts, endothelium).
- Desmin in muscle cells forms the scaffold on which actin and myosin contract.
- Neurofilaments are critical for neuronal axon structure and confer both strength and rigidity.
- Glial fibrillary acidic protein is expressed in glial cells.
- Cytokeratins are expressed in epithelial cells. There are at least 30 distinct different cytokeratins that are expressed in different cell lineages (e.g., lung vs. gastrointestinal epithelium).
- Lamins are intermediate filament proteins that form the nuclear lamina, define nuclear shape, and can regulate transcription.
Growth factors involved in proliferation of hepatocytes?
- Transforming growth factor-α (TGF-α)
- Hepatocyte growth factor (HGF) (scatter factor)
One GF not involved in proliferation?
Transforming growth factor-β (TGF-β)
GFs involved in stimulating proliferation of endothelial cells?
- Vascular endothelial growth factor (VEGF)
- Platelet-derived growth factor (PDGF)
GF involved in increasing vascular permeability?
Vascular endothelial growth factor (VEGF)
GFs involved in chemotaxis for fibroblasts?
- Platelet-derived growth factor (PDGF)
- Fibroblast growth factors (FGFs) including acidic (FGF-1) and basic (FGF-2)
- Transforming growth factor-β (TGF-β)
GF involved in suppressing acute inflammation?
Transforming growth factor-β (TGF-β)
GF involved in stimulating angiogenesis?
Fibroblast growth factors (FGFs) including acidic (FGF-1) and basic (FGF-2)
GFs involved in ECM protein synthesis?
- Platelet-derived growth factor (PDGF)
- Fibroblast growth factors (FGFs) including acidic (FGF-1) and basic (FGF-2)
- Transforming growth factor-β (TGF-β)
Which type of collagen is nonfibrillar?
Type IV
List different steps in the cell cycle and their respective role.
- G1 (gap 1): growth in mass, centrosome duplication, restriction point
- G1/S checkpoint: check for DNA damage (monitors DNA integrity before irreversibly committing cellular resources to DNA replication)
- S (DNA synthesis): chromosome duplication
- G2 (gap 2)
- G2/M checkpoint: check for damaged or unduplicated DNA (insures that there has been accurate genetic replication before the cell actually divides)
- and M (mitotic) phases
