Cells - cell contacts and signalling (mammalian biology)

How do cells form cell-cell contact?

• Cells in an epithelium establish tight lateral and basal contact

• Connections can be viewed using microscopy

What are cells held together by?

• Tight junctions

• Adherens junctions

• Gap junctions

• Desmosomes

• Hemidesmosomes

How do tight junctions hold cells together?

• Function as a diffusion barrier - prevents free diffusion into the cell

• Holds cells together

• Consists of plasma-membrane proteins that interact

How do Adherens junctions hold cells together?

• Consist of cadherin and catenin

• Cadherins bridge between the cells

• Catenins link to the actin cytoskeleton

• Appear to be involved in controlling actin organisation in epithelial cells

How do gap junctions hold cells together?

• Field of connecting channels, each made of connexins

• Channel allows passage of ions and small molecules (1-2nm in diameter)

• Supports exchange between the cytoplasms of adjacent epithelial cells

How do desmosomes hold cells together?

• Contains specialised catherin proteins

• Catherin proteins will interact with each other and intermediate filaments (cytoskeleton)

• Resist shear force in epithelia and in muscle

How do hemidesmosomes hold cells together?

• Contain many proteins (including integrins) that interact with the extracellular matrix

• Present in skin epithelial cells

• Anchor the epithelial cells to the basal lamina (extracellular matrix underneath the epithelium)

• Likely involved in signalling

What are the fundamental steps in cell signalling?

• Signal perception

• Intracellular signal transduction

• Cellular response

What are the components of a cell signalling pathway?

• Extracellular signal molecule

• Receptor protein

• Intracellular signalling protein

• Effector proteins (metabolic, gene regulatory, cytoskeletal proteins)

What are proteins that modify other enzyme activity?

• Kinases phosphorylate other proteins

• Phosphatases dephosphorylate other proteins

• About 30% of all human proteins carry a phosphate group

• Human genome contains 520 kinases and 150 protein phosphatases

How does cell signalling occur through phosphorylation and dephosphorylation?

• Many protein kinases get phosphorylated themselves - amplifies and spreads the signal to other pathways

• Kinases often form a signalling cascade

• Phosphorylated kinases and phosphatases can control the activity of effector proteins

How does signalling via GTP-binding proteins occur?

• G-proteins are molecular switches

• Proteins are activated by a Guanine Exchange Factor (GEF)

• Proteins are inactivated by a GTP-ase Activating Protein (GAP)

• Small monomeric G-proteins will receive signals from many receptors

• Large trimeric G-proteins will interact with G-protein-coupled receptors

What is the structure of ribosomes?

• Prokaryotic 70S ribosome contains a 50S large subunit and 30S small subunit

• Eukaryotic 80S ribosome contains a 60S large subunit and 40S small subunit

What is the mechanism of protein translation?

• Match tRNA to mRNA codon

• Release elongation factor TU

• Form a peptide bond

• Elongation factor G triggers a forward movement

What is the size of the nucleus inside a mammalian cell?

• 2-10 micrometre diameter

• 10% of cell volume

What is the structure of a nuclear pore?

• Highly ordered multi-protein complex

• Nuclear pore has an eight-fold symmetry

• Numerous proteins build the pore and control nuclear transport

How do nuclear pores act as gates to transport material in and out of the nucleus?

• Net of fibres make the nuclear lamina

• Nuclear lamina protects the nucleus against damage, organises the distribution of nuclear pores and arranges interphase chromosomes

• Small molecules can diffuse in and out of the membranes

• Large molecules (including ribosome subunits) are actively transported through the nuclear pores

How does the structure of nuclear pores and the nuclear lamina change during mitosis?

• Phosphorylation of lamina causes them to disassemble

• Dephosphorylation causes reassembly into two separate nuclei

• Nuclear envelope fragments are fused together

• Enveloped chromosomes are fused to form the two new nuclei

How are molecules transported in and out of the nucleus?

• Depends on small GTPase and soluble import/export receptors

• Importins transport molecules into the nucleus

• Exportins transport molecules out of the nucleus