Cell Compartments and GenomeRina SusilowatiDepartment of Histology and Cell Biology Faculty of Medicine Gadjah Mada University

Levels of structural organizationAtomCellMacromoleculeOrganelleMoleculeTissueOrganOrgan SystemOrganism

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

Different cell phenotypes and how they form

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

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Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

Molecular architecture and functional components of cell membrane

Principal lipids found in biological membranes

Permeability of phospholipid bilayers Gases, hydrophobic molecules, and small polar uncharged molecules can diffuse through phospholipid bilayers. Larger polar molecules and charged molecules cannot.

Glucose transport by intestinal epithelial cells

AquaporinThe structure of aquaporin, a water-channel protein[Adapted from A. Chang et al., 1997, Nature 387:627.]

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

GenomeTotal genetic information stored in the chromosomesHuman genome: 3x109 nucleotide pairs24 different DNA molecules in the nucleus of human cells

The export and degradation of misfolded ER proteins

Utilization of different coats in vesicular traffic. Different coat proteins select different cargo and shape the transport vesicles that mediate the various steps in the biosynthetic- secretory and endocytic pathways. When the same coats function in different places in the cell, they can incorporate different coat protein subunits that modify their properties (not shown). Many differentiated cells have additional pathways beside those shown in this figure, including a sorting pathway from the trans Golgi network to the apical surface in polarized cells and a specialized recycling pathway for proteins of synaptic vesicles in the synapses of neurons

Clathrin-coated pits and vesicles. This rapid-freeze, deep-etch electron micrograph shows numerous clathrin-coated pits and vesicles on the inner surface of the plasma membrane of cultured fibroblasts. The cells were rapidly frozen in liquid helium, fractured, and deep-etched to expose the cytoplasmic surface of the plasma membrane. (From J. Heuser, J. Cell Biol. 84:560 583, 1980.

Three pathways to degradation in lysosomes. (A) Each pathway leads to the intracellular digestion of materials derived from a different source. (B) An electron micrograph of an autophagosome containing a mitochondrion and a peroxisome. (B, courtesy of Daniel S. Friend, from D.W. Fawcett, A Textbook of Histology, 12th edn. New York: Chapman and Hall, 1994.)

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

Mitochondria and cellular energy

PeroxisomeOxidative reaction that produces hydrogen peroxide (H2O2 )Catalase utilizes the H2O2 to detoxify various toxin H2O2 + R H2 R + 2H2O - oxidation: converting the fatty acids to acetyl CoA

catalyze the first reactions in the formation of plasmalogens myelin synthesis

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

The cell cycle and cell divisionPhases of the cell cycle in bone tissue. Junqueira Basic Histology

What makes a cell decide to commit suicide?A normal physiological response to specific suicide signals or lack of survival signals

Apoptosis - Falling off - Programmed cell death cell suicide

Cytoplasmic shrinks without membrane rupture

To be engulfed by phagocytes

No spllilage, no inflammation

Cell apoptosis can be induced either through caspase-2 or caspase-3 activationApoptosis is a normal self-destruction mechanism

Signaling systems permit proliferation and apoptosis to be coordinated within a population of cells

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

The cytoskeleton

Figure 11.45. Microtubule motor proteins Kinesin and dynein move in opposite directions along microtubules, toward the plus and minus ends, respectively. Kinesin consists of two heavy chains, wound around each other in a coiled-coil structure, and two light chains. The globular head domains of the heavy chains bind microtubules and are the motor domains of the molecule. Dynein consists of two or three heavy chains (two are shown here) in association with multiple light and intermediate chains. The globular head domains of the heavy chains are the motor domains.

Transport of vesicles along microtubules Kinesin and other plus end-directed members of the kinesin family transport vesicles and organelles in the direction of microtubule plus ends, which extend toward the cell periphery. In contrast, dynein and minus end-directed members of the kinesin family carry their cargo in the direction of microtubule minus ends, which are anchored in the center of the cell.

The surface of an ependymal cell contains basal bodies (arrows) connected to the microtubules of cilia, seen here in longitudinal section. Several microvilli are also present. 37,000

Movement of microtubules in cilia and flagella The bases of dynein arms are attached to A tubules, and the motor head groups interact with the B tubules of adjacent doublets. Movement of the dynein head groups in the minus end direction (toward the base of the cilium) then causes the A tubule of one doublet to slide toward the base of the adjacent B tubule. Because both microtubule doublets are connected by nexin links, this sliding movement forces them to bend.

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

Cell junction, cell-cell adhesion and extracellular matrix

Major families of cell-adhesion molecules (CAMs).

Adhesion molecules in junctions involved in cell-cell adhesion. Adherens junctions and desmosomes are specialized cell-cell junctions that consist of clustered-cadherin dimers. Cadherin is connected to either the circumferential belt of actin filaments or bundles of keratin filaments in the cytoskeleton through the catenin adapter proteins.

Adhesion between leukocytes and endothelial cells

Structure of gap junctions. (a) In this model, a gap junction is a cluster of channels between two plasma membranes that are separated by a gap of about 2 3 nm. (b) Both membranes contain connexon hemichannels, cylinders of six dumbbell-shaped connexin subunits. (c) Each connexin subunit has four transmembrane a helices. Two connexons join in the gap between the cells to form a gap-junction channel, 1.5 2.0 nm in diameter, that connects the cytoplasm of the two cells.

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

Molecular mechanism in signal transduction: basic cell signalling pathways

The nuclear receptor superfamily

Three classes of cell-surface receptors

Various responses induced by the neurotransmitter acetylcholine

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors

Molecular Basis of Medical Cell Biology ContentsDifferent cell phenotypes and how they formStructure and function of intracellular organellesMolecular architecture and functional components of cell membraneOrganelles & vesicle trafficMitochondria and cellular energyThe cell cycle and cell divisionThe cytoskeletonCell junction, cell-cell adhesion and extracellular matrixMolecular mechanism in signal transduction: basic cell signalling pathwaysCell signalling pathways: communication via enzyme-linked and enzyme associated receptors