Medicine Level 1 Physiology: Cellular Communication SGD -Receptors -Messengers -enzymes -Signal Transduction Pathway

1. h e l l o .

4. SGD

5. CELLULAR
COMMUNICATION

6. PROBLE
M

7. Recentincrease in the rate of weight gain
PronetoMusclecramps
Fingersand Toes“Felt Funny”
Child seems listless at times and was rarely veryactive
Motheris veryshortand overweight
WHAT WE
COLLECTED

8. Deficiency
of Thyroid
Hormone

9. TYPES OF
RECEPTO

10. Ligand-GatedIon Channel

11. G-Protein-Coupled Receptor

12. Enzyme-Linked Receptor

13. Intracellular/Nuclear Receptor

14. Specificity

17. affinity

20. SATURATIO
N

21. This refers to the degreeto which receptorsareoccupiedby m
essengers.
 If all are occupied,the receptors are fullysaturated; if
half are occupied,the saturation is 50%, and so on.

24. COMPETITIO
N

25. The ability of different molecules to co
mpete with a ligand for binding to its re
ceptor.
Competitors generally are
similar in structure to the
natural ligand.

26. ANTAGONIS
T /ANTAGONIs
m /

27. Examples:
1. Antihistamines
2. Beta-adrenergic receptor blocker

28. Agonist /
Agonism /

29. Example:
Phenylephrine

30. DOWN-REGULATI
ON &
UP-REGULATION

31. 2 METHODS FORREGULATION OF RECEPTORS:

32. DOWN REGULATION
Prolong exposure of HIGH
messenger conc. on ECF
INTERNALIZATION –
receptor-mediated
endocytosis then degrade
DECREASE no. of target
cell receptors
DESENSITIZING –
reducing
responsiveness

33. INSULIN H DOWN-REGULATION
Due to the elevated levels of blood glucose
in an overweight individual, the β-
cells (islet of Langerhans) in the pancreas
must release more insulin than normal
The near-constant increase in blood
insulin levels results from an effort to
match the increase in blood glucose
Cause receptor sites on the liver cells to
downregulate and decrease the number of
receptors for insulin.
Decreasing sensitivity to this hormone.
Common process of “insulin resistance”
which leads to adult-onset diabetes

34. UP-REGULATIONProlong exposure of
LOW messenger
conc. on ECF
Recruitment of
intracellular vesicle
with lots of receptors
INCREASE no. of target
cell receptors
DESENSITIZING –
reducing
responsiveness

35. NEUROTRANSMITTER UP-REGULATION
Nerves to a muscle are damaged.
Delivery of neurotransmitters from those nerves
to the muscle is decreased or eliminated.
With time, under these conditions,
the muscle will still contract in
response to a much smaller amount
of neurotransmitter than normal.
This happens because the receptors
for the neurotransmitter have been
up-regulated, resulting in increased
sensitivity.

36. SIGNAL
TRANSDUCTI
ON

37. Signal Transduction
the conversion of an extracellular message
(stimulus) into an intracellular signal which
initiates a series of events that ultimately ends
with the cell’s response to the initiating stimulus
Signal: receptor activation
 Transduction: transformation of stimulus into a
response

38. Receptor activation: The binding of a
messenger to its receptor causes a change in
the conformation (tertiary structure) of the
receptor (Widmaier, et al. 2016)

40. 2 Major Pathways
1. Lipid-soluble messenger initiated pathways
Example: Intracellular/ nuclear receptor pathways
2. Lipid-insoluble messenger initiated pathways
Example: Ionotropic channel pathways
Catalytic receptor pathways
G protein-coupled receptor pathways

41. Signal Transduction Steps
1. RECOGNITION - binding of ligand to receptor; one
signaling molecule can sometimes bind to more than one
kind of receptor
- Ligand-receptor bonds:
a. Ionic bonds - between groups of opposite charge
b. Van der Waals interactions - transient dipole in one
atom generates the opposite dipole in an adjacent
atom
c. Hydrophobic interactions - between nonpolar groups

42. 2. TRANSDUCTION - transformation of
extracellular msg into intracellular signal or
second messenger
- ligand binding causes conformational change
receptor which activates the receptor depending
on its type
- can also involve the generation of second
messenger or activation of catalytic cascade

43. 3. TRANSMISSION - transmission of second
messenger’s signal to effector (can be enzymes, ion
channels, and transcription factors)
4. MODULATION OF EFFECTOR - effectors can
activate or deactivate other proteins such as kinases and
phosphatases
5. RESPONSE - response of cell to initial stimulus;
collection of actions which represent the summation and
integration from multiple signaling pathways

44. 6. TERMINATION - cessation/conclusion of
response through feedback mechanisms at
any or all levels of signaling pathway.

45. Other Ways Cells Communicate
1. GAP JUNCTIONS - facilitate the passage of inorganic
ions and small molecules, such as Ca2+ and 3′,5′-cyclic
adenosine monophosphate (cAMP), from the cytoplasm
of one cell into the cytoplasm of an adjacent cell.
- Involves proteins called connexins

47. 2. ADHERING / TIGHT JUNCTIONS - Provide
important clues for the maintenance of normal cell
architecture as well as the organization of groups of
cells into tissues.
- Involves cadherins, catenins, and actin
cytoskeleton

49. binding of lipid-soluble
messengers to
receptors

51. Binding of
lipid-insoluble (
water-soluble)
messengers to
receptors

52. Signal transduction mechanism in which the receptor
complex includes an ion channel

53. Signal transduction mechanism in which the receptor itself
functions as an enzyme

54. Signal transduction mechanism in which the receptor
activates a janus kinase in the cytoplasm

55. Signal transduction mechanism involvingG proteins

56. G Protein
activation

57. Overview of the key components
1. G-Protein-Coupled Receptors // GPCR
A family of receptors that detect molecules outside the cell
and activate internal signal transduction pathways leading
to a cellular response.
Other names: serpentine receptor, G protein-linked receptors
(GPLR), 7TM receptors, seven-(pass)-transmembrane domain
receptors, heptahelical receptors.

58. 2. Guanine nucleotide-binding proteins //
“G proteins”
A trimeric protein that acts as molecular switch
located in the cytosolic portion of the cell and are
involved in transmitting signals from a variety of
stimuli outside a cell to the interior of the cell.

60. Signal Transduction and/ Key events
1. GPCR activation by a ligand
2. Alpha subunit activation
3. Alpha subunit links up with an ion or enzyme
4. Cell response
5. Alpha subunit inactivation

61. First messengers
• Extracellular messenger
(such as hormones and
neurotransmitters) that
reach the cell and bind to
their specific plasma
membrane receptors
Second Messengers
• Substances that enter or are
generated in the cytoplasm as
a result of a receptor activation
by the first messenger
• Diffuse throughout the cell to
serve as chemical relays from
the plasma membrane to the
biochemical machinery inside
the cell

62. cAMP Activation
• Binds to and activates cAMP-dependent
protein kinase
• The activation of adenylyl cyclase by the
𝐺8 initiates an “amplification cascade” that
converts proteins from inactive to active
state

63. While active,single enzyme
moleculeis capableof
transforming many substrate
molecules

64. cAMP Activation
• Protein Kinase phosphorylates proteins that
then binds to specific regulatory regions of
certain genes
• Can result to rapid and independent
changes in gene activity

65. • Activation of protein kinase is common among
biochemical reactions initiated by cAMP generating
first messenger because it can phosphorylate a
large number of different proteins.
• The protein kinase can exert multiple actions
within a single cell and different actions in
different cells

66. • Some receptors of first messengers inhibit aldenylyl
cyclase
• The activation protein is 𝑮𝒊 (i stands for
“inhibiting” and s stands for “stimulatory”
•
Decreases concentration of cAMP and the
phosphorylation of key proteins in the cell
• Many cells express both 𝑮𝒊 and 𝑮 𝒔 to regulate
intracellular cAMP concentrations

67. Protein kinase can phosphorylate certain
plasma membrane ion channels, causing them
to open or close

68. Phospholipase C, Diacylglycerol,
and Inositol Triphosphate

69. 𝑪𝒂 𝟐+
 Increase in cytosolic 𝑪𝒂 𝟐+
concentration
 Induction of Cell Response

70. Increase in cytosolic 𝐶𝑎2+
concentration
Receptor activation
• Plasma-membrane 𝑪𝒂 𝟐+ channels open in response to a first
messenger; the receptor itself may contain the channel, or the
receptor may activate a G protein that opens the channel via a
second messenger
• 𝑪𝒂 𝟐+ is released from the endoplasmic reticulum; this is typically
mediated by 𝑰𝑷 𝟑
• Active 𝑪𝒂 𝟐+ transport out of the cell is inhibited by a second
messenger
Opening of voltage-gated 𝑪𝒂 𝟐+
channels

71. Induction of Cell Response
• 𝑪𝒂 𝟐+
binds to calmodulin. On binding 𝑪𝒂 𝟐+
, the
calmodulin changes shape and becomes
activated, which allows it to activate or inhibit
a large variety of enzymes and other proteins.
Many of these enzymes are protein kinases
• 𝑪𝒂 𝟐+
combines with 𝑪𝒂 𝟐+
-binding proteins
other than calmodulin, altering their functions.

72. Thankyou