Lecture 10: General Principles of Cell Signalling

Question 1

signalling molecules are synthesized and released by _______ and produce a specific response only in ______ that have _______ for the signalling molecules.

Answer 1

signalling cells, target cells, receptors.

Question 2

Define signal transduction

Answer 2

the process of converting an extracellular signal
into an intracellular signal in a target cell in which initiates a series of intracellular reactions that regulate metabolism, movement, proliferation, survival, and differentiation of the target cell.

Question 3

Name six steps in signalling transduction

Answer 3

1) synthesis of signalling molecule by signalling cell.
2) release of signalling molecule by signalling cell.
3) transport of the signalling molecule to the target cell.
4) detection of the signal by specific receptor protein.
5) a change in cellular metabolism, function, or development triggered by the receptor-signalling molecule complex.
6) removal of the signalling molecule, which terminated the cellular response.

Question 4

Cell signalling is based on:

Answer 4

• the distance in which the signal molecule reacts.
• the speed in which the signal molecule is delivered to the target cell.
• the selectivity with which the signal molecule is delivered to the target cell.

Question 5

Five types in which cell signalling is classified

Answer 5

endocrine, paracrine, autocrine, neuronal, direct (contact-dependant) cell signalling.

Question 6

Define endocrine signalling

Answer 6

• signalling molecules: hormones.
• hormones produced in endocrine cells are secreted into bloodstream distant from their site of synthesis by endocrine cells.

Question 7

Define paracrine signalling

Answer 7

• signalling molecules released into extracellular medium act locally to affect target cells in close proximity.

Question 8

Define autocrine signalling

Answer 8

• cells respond to signalling molecules they themselves release.
• common in cancer cells, overproduce and release growth factors that stimulate unregulated growth and division of themselves.

Question 9

Define neuronal signalling

Answer 9

• signals transmitted from the cell body of a neuron (nerve cell) along the axon to remote target cells.
• when activated by signals from the environment or other nerve cells, the neuronal cell body sends electrical impulses along the axon (100 m per second).
• the intracellular electrical signals stimulate the axon terminal to secrete extracellular signalling molecules called neurotransmitters.
• target cell needs specific neurotransmitter receptors.

Question 10

Direct signalling

Answer 10

• signal molecule is anchored in the plasma membrane of the signalling cell binds to a receptor molecule embedded in the plasma membrane of the target cell.
• requires a membrane to membrane contact.
• does not require the release of a signal molecule.

Question 11

Name types of extracellular signal molecules

Answer 11

1- large hydrophilic: largest class, too large and hydrophilic to cross membrane, requires outer surface of plasma membrane.
2- small lipophilic : sufficiently small to diffuse across plasma membrane, receptors located in the of target, either in cytosol or nucleus.

Question 12

Extracellular signal molecules bind to outer surface receptors which in turn

Answer 12

convert extracellular signals into intracellular signals which initiate signalling cascades.

Question 13

Role of intracellular signalling cascades

Answer 13

• amplify, distribute (to several intracellular targets) and diverge the signals received.

Question 14

Describe the multiple steps in intracellular signalling cascades

Answer 14

1) primary step: receptor on cell surface receives extracellular signal (ligand) and generates a new intracellular signal.
2) secondary (downstream) step: the intracellular signal initiate signalling cascades.

Question 15

Types of intracellular signalling molecules

Answer 15

low molecular weight molecules (2nd messengers) such as cAMP, Ca2+ and proteins.

Question 16

Signalling cascades can be influenced by other events inside or outside the cell (T/F)

Answer 16

T.

Question 17

Name three types of ligand triggered cell surface receptors

Answer 17

G-protein-linked, ion-channel-linked, enzyme-linked.

Question 18

Describe steps in G-protein-linked receptors

Answer 18

1- receptor binds to ligand.
2- receptor interacts with inactive GTP-binding protein and activates it.
3- G-binding protein leaves receptor, binds to innactive effector enzyme, and activates it.
5- activated effector enzyme generates specific 2nd messenger.

Question 19

Describe steps in Ion-channel-linked receptors

Answer 19

1- binding of ligand changes receptor conformation, opens channel, and ions flow in.
2- changes in concentration of intracellular ions triggers processes in target cell.

Question 20

Describe steps in enzyme-linked receptors

Answer 20

binding of the ligand turns on enzyme activity on the opposite side of the plasma membrane.

Question 21

Signalling cascades are formed by

Answer 21

intracellular signalling proteins acting as switches.

Question 22

Name 3 classes of intracellular switches

Answer 22

(1) Protein phosphorylation –dephosphorylation.
(2) GTP binding –hydrolysis.
(3) Assembly – disassembly of multiprotein complexes.

Question 23

Define dephosphorylation switches

Answer 23

Switches between active and inactive state depending if its phosphorylated or not. Protein kinase activates the switch by phosphorylating it, and protein phosphatase inactivates the switch by dephosphorylating it.

Question 24

Many switch proteins controlled by phosphorylation are themselves

Answer 24

protein kinases and organized into phosphorylation cascades, one protein kinase phosphorylates the next protein kinase (onward signal).

Question 25

Define hydrolysis switches

Answer 25

GTP-binding protein is activated when bound to GTP and inactive when bound to GDP. In the absence of a signal, it is bound to GDP, and in the presence of a signal activates the release of GDP and binding of GTP. The GTPase of these switches hydrolyse GTP, converting active form back to inactive.

Question 26

Define assembly switches

Answer 26

• Multiprotein signalling complexes held together by adapters. Ligand binding induces interacting of receptor with an adapter protein.
• Adapter proteins contain different combinations of domains, which function as docking sites for numerous intracellular signalling proteins (switches) and promote the formation of multiprotein complexes.

Question 27

Name 3 locations of lipophilic receptors

Answer 27

(1) nucleus
(2) signalling molecule-receptor complex transported into nucleus or
(3) remains in cytosol.

Question 28

Types of lipophilic intracellular receptors and FIRST GROUP lipophilic signalling molecules

Answer 28

Family of steroid receptor superfamily and transcription factors (activate or repress transcription of target genes).
lipophilic molecules include:
1) steroid hormones (synthesized from cholesterol): testosterone, cortisol.
2) thyroid hormones: thyroxine.

Question 29

Define the domain(s) of steroid hormone receptors

Answer 29

Bind DNA as dimers and contain four domains such as; ligand binding, DNA binding, dimerization, transcription activation.
(in this order)

Question 30

Steps in gene regulation by the steroid hormone cortisol and its receptor

Answer 30

step 1:

• cortisol binds to receptor in cytosol.
• binding of cortisol induces conformation change of receptor which is now able to; be transported in the nucleus, bind to specific regulatory sequences of cortisol-inducible genes.

step 2:
cortisol-receptor complex transported into nucleus via NPCs.

step 3:
- in nucleus activated cortisol-receptor complexes form dimers, bind to specific regulatory cortisol-inducible genes, and activate transcription of these genes.

Question 31

Steps in gene regulation by the thyroid hormone thyroxine and its receptor

Answer 31

step 1:
Thyroxine diffuses directly across the plasma membrane.

step 2:
Thyroxine is transported into the nucleus via the nuclear pores.

step 3:

• thyroxine binding changes the function of the thyroid hormone receptor (present in nucleus).
• receptor goes from a repressor to an activator of transcription of thyroid-inducible genes.
• the receptor binds to DNA in the presence or absence of thyroxine.

Question 32

Types of lipophilic intracellular receptors and SECOND GROUP lipophilic signalling molecules

Answer 32

• Arginine converted to citrulline and nitric oxide with the help of NOS (nitric oxide synthase) hydrolyzing 02+NADPH to NADP and one double bonded O to citrulline and the other to nitric oxide.
• nitric oxide receptor is in the cytosol, is the enzyme guanylyl cyclase, which generates the 2nd messenger cGMP.

Question 33

Function of cGMP causes

Answer 33

smooth muscle cells in a blood-vessel wall to relax,

so that the blood can flow more freely through the vessel.