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2.1 Introduction

This section reminds you of the numerous specialised intracellular compartments of the eukaryotic cell, with how molecules are moved rapidly and specifically between them in eukaryotic cells.

  • What are the principal membrane-bound compartments of the cell and the trafficking pathways that connect them?

  • Early and late end
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1.5 Summary

  1. The cytoskeleton is formed of microtubules, microfilaments and intermediate filaments. Microtubules are formed by polymerisation of tubulin and microfilaments by polymerisation of actin. Assembly and disassembly are faster at the plus end of the filament. Both microtubules and microfilaments can display treadmilling and dynamic instability, in appropriate conditions.

  2. Actin is an ATPase, and actin-ATP is less readily dissociated from the ends o
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1.2 Polymerisation and depolymerisation of actin

Actin is a highly conserved protein. Most organisms have several genes encoding actin; in humans there are six principal isoforms, four of which are found in different types of muscle and the other two (β and γ) in all non-muscle cells. (The term ‘isoform’ describes variants of a protein. These may be produced by different genes, or by differential splicing of the mRNA, or be generated by post-translational modifications.) The β and γ cytoskeletal forms differ by just four amino acid
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1.1 Microtubules and microfilaments

The elements of the cytoskeleton each have their own distribution within the cell. Microtubules extend from the microtubule organising centre (MTOC), which in animal cells is the centrosome, usually located close to the nucleus. The centrosome consists of two centrioles, short cylinders of microtubules arranged at 90° to each other, which are embedded in a matrix of protein (Author(s): The Open University

Learning outcomes

By the end of this unit you should be able to:

  • define and use each of the terms printed in bold in the text.

  • describe the characteristics of different intracellular compartments with respect to their structure, location and composition within a mammalian cell;

  • describe the traffic pathways between the endoplasmic reticulum, the Golgi apparatus, the endosomal compartments, and the basolateral and apical regions of the plasma membrane;


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Introduction

The cytoskeleton is of fundamental importance to a cell, and the development of different elements of the cytoskeleton were key steps in the evolution of eukaryotic cells. The cytoskeleton controls cell shape and allows cell movement; it is required for many aspects of intracellular trafficking of vesicles and organelles, and it is involved in cell division. Because of its important role in facilitating the movement of vesicles between compartments, but a basic understanding of how the cytosk
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Acknowledgements

Grateful acknowledgement is made to the following sources for permission to reproduce material in this unit:

This content is made available under a Creative Commons Attribution-NonCommercial-ShareAlike 2.0 LicenceSee Terms and Conditions

Figures

Figure: 1 Copyright
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3.9 Summary

  1. Heterotrimeric G proteins are tethered to the internal surface of the plasma membrane, and are activated by conformational change within 7TM receptors. There are many different α subunits (and a few βγ subunits), which interact with different receptors and different effectors. The major targets of G proteins include ion channels, adenylyl cyclase (activated by Gαs and inhibited by Gαi) and PLC-β (activated by Gαq).


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3.6.2 The JAK–STAT pathway

Another important protein kinase pathway is the JAK–STAT pathway. Cytokines (Section 2.2), are frequently used for signalling between cells of the immune system. Cytokine-induced signal transduction cascades are often direct pathways to the nucleus for switching on sets of genes. Janus kinases (JAKs, named after the two-faced Roman god) are a particular
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3.4.3 Cyclic GMP

Cyclic GMP (cGMP) is a second messenger with many similarities to cAMP. It is synthesized from GTP by guanylyl cyclase, and degraded to 5´- GMP by cyclic GMP phosphodiesterases. Some of the targets of cGMP are analogous to those of cAMP: cGMP-dependent protein kinase (PKG), and cGMP-gated Na+ ion channels.

  • We have already discussed a type of rece
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3.4.2 Cyclic AMP

The concentration of cyclic AMP (cAMP) in the cytosol increases 20-fold within seconds of an appropriate stimulus. This is achieved by the action of the plasma membrane-embedded protein adenylyl cyclase, which synthesizes cAMP from ATP (Figure 34). cAMP is short-lived, as with all second messengers, because it is continuously degraded by
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3.4.1 Calcium ions

The Ca2+ concentration is normally low in the cytosol (~10–7 mol 1–1) compared with the extracellular space (~10–3 mol 1−1). There are several mechanisms for achieving this. The most widespread are ATP-dependent Ca2+ efflux pumps on the plasma membrane, which pump Ca2+ ions out of the cell. Muscle and nerve cells, where oscillations in intracellular Ca2+ concentration often occur, employ an additio
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3.4 Second messengers

In the previous section, we have discussed the principles of second messengers (Section 1.5) and, in particular, those produced by PLC (IP3 and DAG) and PI3 kinase (PI(3,4)P2 and PI(3,4,5)P3). We shall now consider the roles and mechanisms of action of the other chief mediators, which are Ca2+ ions, cAMP and cGMP
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3.3.2 Phospholipase C (PLC)

Members of this family of enzymes contain two catalytic domains and several protein binding domains (Figure 13). The PH domain can temporarily tether phospholipase C to the membrane by attachment mainly to PI(3,4)P2.

We shall discuss two main isoforms of PLC: PLC-β, which is activated by a subset of trimeric G proteins (Gαq an
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3.3.1 Phosphatidylinositol 3-kinase (PI 3-kinase)

Members of this family of lipid kinases usually have two subunits: one is a catalytic subunit with a lipid kinase domain and the other is a regulatory subunit, which contains two SH2 domains and a SH3 domain (p 85 PI 3-kinase in Figure 13).

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3.3 Lipid-modifying enzymes

The internal surface of the plasma membrane provides a useful environment for spreading signals received by surface receptors around the cell. Several specialist enzymes are activated by membrane-bound receptors, creating large numbers of small lipid-soluble second messenger molecules, which can diffuse easily through the membrane. These enzymes all use phosphatidylinositol (PI) and its derivatives as their substrates. PI itself is a derivative of glycerol: the OH group on carbon atom
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3.2 Trimeric G proteins

G proteins are attached to the cytosolic face of the plasma membrane, where they serve as relay proteins between the receptors and their target signalling proteins.

Trimeric G proteins interact with 7TM receptors and are all heterotrimeric, having structurally different α, β and γ subunits. Monomeric G proteins are the small G proteins, such as Ras, which are structurally related to the α subunit of trimeric G proteins.

The three-dimensional structure of trimeric G proteins in
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3.1 Introduction

We are now ready to describe in detail the major intracellular signalling pathways responsible for relaying the signal from the surface receptor to evoke a cellular response. This section will deal with signalling molecules that operate at the cytosolic leaflet of the plasma membrane (trimeric G proteins, monomeric G proteins and lipid-modifying enzymes), second messengers (such as Ca2+, cAMP, cGMP), protein kinases and phosphatases, and finally transcription factors.


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2.6 Summary

  1. Receptors comprise a limited number of structural motifs, which determine binding affinity and specificity of receptor–ligand complexes. Some ligands bind to several receptors and some receptors bind to several ligands.

  2. Acetylcholine is a good example of a ligand with two structurally different kinds of receptor. Nicotinic receptors are ion channels, which are found predominantly in skeletal muscle, and are stimulated by nicotine. Nicotinic
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2.5 Intracellular receptors

Signal receptors are usually located at the cell surface. However, it is important to remember that there are some groups of receptors that do not fit into the general signal transduction model set out in Figure 2, These are intracellular receptors, which bind small or lipophilic molecules such as steroid hormones, which can cross the cell membrane. The signalling pathways activated by these receptors seem quite simple compared with the other pathways we shall be dealing with, but the same pr
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