2.0 Cell Communication and Signalling

Question 1

Define 2 types of direct intercellular signalling

Answer 1

1. Contact dependent signalling =

requires cells to be in direct membrane-membrane contact. Direct transfer of electrical or chemical signals through gap junctions allowing ion flow to pass directly from cell to cell (e.g.in heart muscle and smooth muscle), and small ions and molecules to be exchanged directly between the cytoplasm of interacting cells without ever entering the extracellular fluid.

2.Transient direct link-up =
between cells is a specialised signalling process that occurs when identifying markers on the plasma membrane of two particular cells link up e.g. when phagocytes of the immune system recognise and selectively destroy undesirable cells, such as cancer cells and when cell adhesion molecules (CAMs) transfer signals across cell membranes.

Question 2

Outline the mechanisms of intercellular chemical signalling in the autocrine, paracrine, and endocrine systems

Answer 2

Paracrine signalling (para- beside; krinen- to secrete) is a form of indirect signalling that depends on local mediators that are released into the extracellular space and act on neighbouring cells (e.g. histamine and leukotrienes released from mast cells bind to nearby cells)

Autocrine signalling (auto- self) is a signal that acts on the cell that secreted it

Endocrine signalling depends on endocrine cells which secrete hormones into the bloodstream for long-range distribution throughout the body to cells that express the membrane receptor for the particular hormone

Neuroendocrine (neurohormonal) signalling is performed by neurons that transmit signals electrically along their axons, releasing hormones into the bloodstream by neurosecretory neurons

Question 3

Outline how the hypothalamus-pituitary-thyroid (HPT) axis exemplifies neuroendocrine and endocrine systems

Answer 3

The Hypothalamus-Pituitary-Thyroid Axis (HPT axis) is one system that exemplifies both neuroendocrine and endocrine systems.

• the hypothalamus is a gland portion of the brain that secretes neurohormones. In the HPT axis this hormone is called Thyrotropin Releasing Hormone (TRH).
• hypothalamic neurohormones are released into a local blood vessel system, called the portal system, to reach the pituitary gland.
• neurohormones act on the endocrine cells in the pituitary to release hormones directly into the body’s circulation
• an example is Thyroid Stimulating Hormone (TSH). Its target is the thyroid gland (which controls protein, carbohydrate and fat metabolism).

Question 4

Distinguish between electrical and chemical signalling and identify an example of each

Answer 4

Neurons communicate at synapses, i.e. between the presynaptic cell and the membrane of the postsynaptic cell. The two types of synapses are

1.Electrical synapses, which pass electrical current from the cytoplasm of one cell to that of another through gap junctions. They are mainly found in the central nervous system (brain and spinal cord), heart and smooth muscle.

2.Chemical synapses, which use neurocrine molecules to carry electrical signals from the presynaptic neuron across the synaptic cleft to the receptor on the target cell

Question 5

Describe the role of neurotransmitters in synaptic transmission

Answer 5

Neurotransmitters can bind to ligand-gated (ionotropic) ion channels which are mainly involved in fast (milliseconds) synaptic transmission.

Question 6

Describe the different types of intracellular signalling including those that use second messenger systems

Answer 6

Intracellular receptors
- are found in either the nucleus or the cytosol
- binding with their ligand allows for the binding of the complex to defined regions of DNA (DNA binding domains), causing changes in transcription and mRNA production
- cellular response, due to altered protein synthesis, is slow (hours to days)
- examples include receptors for steroid hormones (e.g. cortisol, oestrogen), thyroid hormone, vitamin D.

Question 7

Describe the process of a chemical signalling cascade associated with the activation of voltage-gated Ca2+ channels, with reference to muscle contraction

Answer 7

1. An action potential depolarises the axon terminal
2. Depolarisation opens voltage gated calcium ion channels, calcium ions enter the cell
3. Calcium entry triggers exocytosis of synaptic vesicle contents
4. NT diffuses across synaptic cleft and binds with receptors on the post synaptic cleft
5. NT binding initiates a response in the postsynaptic cleft

Question 8

Provide examples of chemicals that can modulate signals at the neuromuscular junctions and their mechanism of action

Answer 8

1. cAMP
   Made from = ATP
   amplifier enzyme= adenylate cyclase
   linked to= GPCR
   Action= activates protein kinases binds to ion channels
   Effects= phosphorylates proteins, alters channel opening
2. cGMP
   Made from= GTP
   amplifier enzyme= guanylyl cyclase
   linked to = receptor enzyme
   Action= activates protein kinase
   Effects= phosphorylates proteins
3. Inositol triphosphate (IP3)
   Made from= membrane phospholipids
   Amplifier enzyme = phospholipase C (PLC)
   Linked to = GPCR
   Action= releases calcium ions from intracellular stores
   Effects= calcium ions effect such as exocytosis, muscle contraction, channel opening
4. Diacylglycerol (DAG)
   Made from= membrane phospholipids
   Amplifier enzyme= phospholipase C (PLC)
   linked to= GPCR
   Action= activates protein kinase C (PKC)
   Effects= phosphorylates proteins
5. Ca(2+)
   made from= n/a
   amplifier enzyme= n/a
   linked to= n/a
   Action =binds to calmodulin, troponin and other proteins
   Effects= calcium ion effects such as exocytosis, muscle contraction, channel opening

Question 9

Describe the function of acetylcholinesterase in the synaptic cleft and give examples of chemicals that modulate its activity

Answer 9

The primary role of AChE is to terminate neuronal transmission and signaling between synapses to prevent ACh dispersal and activation of nearby receptors.

Question 10

Define 4 types of indirect intercellular signalling

Answer 10

1. Paracrine signalling (para- beside; krinen- to secrete) depends on local mediators that are released into the extracellular space and act on neighbouring cells (e.g. histamine and leukotrienes released from mast cells bind to nearby cells (see “Immunity” lesson). Similarly, autocrine signalling (auto- self) is a signal that acts on the cell that secreted it (e.g. cytokines act as both autocrine and paracrine signals)
2. Neurotransmitter signalling is performed by neurons that transmit signals electrically along their axons, releasing neurotransmitters into the synapses
3. Neurohormonal (neuroendocrine) signalling is performed by neurons that transmit signals electrically along their axons, releasing hormones into the bloodstream by neurosecretory neurons (e.g. adrenaline)
4. Endocrine signalling depends on endocrine cells which secrete hormones into the bloodstream for long-range distribution throughout the body to its target cells that express the membrane receptor for the particular hormone (e.g. thyroid hormone)

Question 11

4 steps of general signal pathways

Answer 11

Signal molecules must exert some chemical influence on one or more constituents of cells in order to produce a response.

Signal pathways share the following steps:

1. A signal molecule is a ligand that binds to a protein receptor. It is also known as the first messenger.
2. Binding of a receptor by a chemical molecule may or may not result in receptor activation. If the signal molecule activates the receptor it is called an agonist.
3. The receptor in turn activates one or more intracellular signal molecules that target or modify expression of a target protein
4. The last signal molecule initiates a response.

Question 12

Brief definition of G protein–coupled receptors (GPCRs)

Answer 12

plasma membrane receptors that indirectly activate (through GTP-binding proteins, or G proteins) enzymes that generate intracellular second messengers, e.g. adenylyl cyclase, cyclic AMP. Example, muscarinic ACh receptors

Question 13

Brief definition of Receptor tyrosine kinases

Answer 13

plasma membrane receptors that are also enzymes. When one of these receptors is activated by its extracellular ligand, it catalyzes the phosphorylation of several cytosolic or plasma membrane proteins.

Question 14

Brief definition of Receptor guanylyl cyclases

Answer 14

plasma membrane receptors with an enzymatic cytoplasmic domain. The intracellular second messenger for these receptors, cyclic guanosine monophosphate (cGMP), activates a cytosolic protein kinase that phosphorylates cellular proteins and thereby changes their activities.

Question 15

Brief definition of Gated ion channels of the plasma membrane

Answer 15

open and close (hence the term “gated”) in response to the binding of chemical ligands (ligand-gated) or changes in membrane potential (voltage-gated).
are the simplest signal transducers and are fast, e.g. nicotinic ACh receptor

Question 16

Brief definition of Adhesion receptors

Answer 16

interact with macromolecular components of the extracellular matrix (such as collagen) and convey instructions to the cytoskeletal system about cell migration or adherence to the matrix.
Integrins illustrate this general type of transduction mechanism and mediate blood clotting and cell adhesion.

Question 17

Brief definition of Nuclear receptors

Answer 17

bind specific ligands and alter the rate at which specific genes are transcribed and translated into cellular proteins.
Steroid hormones (such as the hormone oestrogen) function through mechanisms intimately related to the regulation of gene expression.

Question 18

Define signal transduction

Answer 18

Signal transduction is the process by which an extracellular signal (first messenger) molecule activates a receptor (see previous page) that alters intracellular molecules (second messenger system) to create a response (as shown in figure above).

The signal transduction pathway
- transforms an original signal from a ligand binding to its receptor via a signalling cascade, which converts one or more inactive molecules to an active form inducing a response.
- amplifies the effect of the ligand via amplifier enzymes, which enable a small ligand to create a large effect.

Question 19

Describe G-protein Coupled Receptors (GPCR)

Answer 19

• metabotropic receptors
• highly lipophilic transmembrane segments that cross the phospholipid bilayer
• receptors which are coupled to either a channel or enzyme system within the cell
• receptors for slow transmitters
• guanosine nucleotide–binding protein (G-protein) which activates the effector enzyme, i.e. inactive G-proteins are bound to GDP (guanosine diphosphate), exchanging GDP for GTP (guanosine triphosphate) on the alpha subunit to activate the G-protein.

Question 20

Four Subsequent Possible Effects of G Protein Binding

Answer 20

1. opening an ion channel in the membrane, e.g. a potassium channel that is opened in response to the G protein activation. This channel often stays open for a prolonged time.
2. activating an enzyme system. Activation of cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP) can activate highly specific metabolic machinery in the cell and, therefore, initiate any one of many biochemical reactions including long-term changes in cell structure itself.
3. activating an intracellular enzyme system. The G protein can directly activate one or more intracellular enzymes which, in turn, can cause any one of many specific biochemical reactions in the cell.
4. causing gene transcription. Activation of gene transcription is one of the most important effects of activation of the second messenger systems because gene transcription can cause formation of new proteins within the cell, thereby changing its metabolic machinery or its structure.

Question 21

Describe Ligand-Gated Ion Channels

Answer 21

• are ionotropic receptors
• are transmembrane ion-selective channels
• binding causes a change in the conformation of the channel that increases its permeability to a particular ion
• are receptors for fast transmitters

Question 22

Describe Kinase-Linked Receptors

Answer 22

• are transmembrane receptors with an intracellular domain that is linked to enzymes such as tyrosine kinase or guanylyl cyclase activity
• growth factors, cytokines, and hormones (such as insulin) are signal molecules at these receptors
• play a major role in controlling cell division, growth, differentiation, inflammation, apoptosis, and immune responses