Cell Signaling Flashcards
1
Q
Terminology
A
- Ligand: General term for a molecule that binds to a specific site on a protein
- Receptor: Protein that recognizes and respondsto a signaling molecule(s) (ligand)
- Agonist: Substance (ligand) that interacts with a receptor to initiate a physiological response
- Antagonist: Substance (ligand) that interferes with or inhibits the physiological action of another substance
- Second Messenger: Small intracellular signaling molecule generated or liberated in response to an extracellular signal
2
Q
Key and ock Model of Signaling Molecules and Receptors
A
- Signaling molecules exhibit some 3D structure that is complimetary to the receptor binding site
- Interactions of an agonist with the binding site induces a conformational shift of the receptor to a form that affects cell function
- Antagonists may exhibit structural complementarity to the binding site, or may interact with a different site to change receptor structure, and render the receptor unresponsive to an agonist
3
Q
Signaling Modalities
A
- Cell Coupling
- Contact-Dependent
- Secreted Molecules
4
Q
Gap Junctions
A
- Example:
- Glucagon receptors are not uniformly distributed on cells throughout the liver. Gap junctions couple cell activity
- Signal:
- cAMP (cyclic adenosine monophosphate)
- Function:
- Synchronize response to glucagon
- Example:
- Cardiac muscle cells are electrically coupled
- Signal:
- Electrical conductance
- Function:
- Synchronization of cardiac muscle contraction
5
Q
Contct-dependent Signaling
A
- Example:
- Leukocyte adhesion prior to transmigration during inflammation
- Signal:
- Glycoproteins on the leukocyte
- Receptor:
- Adhesion proteins on endothelial cells
- Function:
- Attract and guide leukocytes to a site o injury
6
Q
Signaling via Secreted Molecules
A
- Classes:
- Hormones, neurotransmitters, autacoids, cytokines
- Signals:
- Vasopressin, acetylcholine, bradykinin, interleukin 2
- Receptors:
- Vasopressin receptor (V2), Nicotinic acetylcholine receptor (nAchR), Bradykinin receptor (B1), Interleukin receptor (IL-2Ra or CD25)
- Function:
- Fluid balance, muscle contraction, vasodilation, immune function
7
Q
Signaling via Secreted Molecules (continue)
A
- Endocrine: Signaing molecule is transported via circulation
- Neuroendocrine: Like endocrine with signaling cell being a neuron
- Paracrine: Signaling molecule diffues through extracellular medium to nearby cell
- Autocrine: Signaling molecule diffuses through extracellular medium, Signaling cell is also a target
8
Q
(Neuro) Endocrine Signaling
A
- Example:
- Vasopressing or Anti-diuretic hormone (ADH)
- Signal:
- Arginine vasopressin
- Receptors:
- V1 Receptor on vascular smooth msucle cells
- V2 Receptor on kidney collecting duct cells
- Functions:
- Increase vascular resistance and blood pressure
- Increase water retention to maintain vascular volume
9
Q
Vasopressin Signaling
A
- Condition:
- Elevated blood osmolality (and/or)
- Low blood volume
- Events:
- Hypothalamic neurosecretory cells respond by releasing vasopressin in posterior pituitary, which enters vasuclar circulation
- V1 receptos on vascular smooth muscle cells are activated to cause cytosolic release of diacylglycerol (DAG) and IP3, which causes contraction
- V2 receptors in nephrons are activated to increase cytosolic cAMP, which induces he insertion of aquaporins allowing water retntion
- Outcome:
- Increased blood pressure
- Stabilize fluid volume/reduce fluid loss
10
Q
Paracrine Signaling
A
- Example:
- Histamine-induced vascular changes
- Signal:
- Histamine and nitric oxide (NO)
- Receptor:
- H1 on vascular endothelial cells
- Smooth muscle guanylyl cyclase
- Functions:
- Vasodilation as a component of an inflammaroty response
11
Q
Neuronal Signaling
A
- Example:
- Neuromuscular junction
- Signal:
- Acetylcholine
- Receptor:
- Nicotinic acetylcholine receptor (nAchR)
- Functions:
- Voluntary muscle contraction
12
Q
Neuromuscular Junction
A
13
Q
Endocrine vs. SYnaptic Signaling
A
- Endocrine:
- Signal reaches most cells
- Low concentrations of the signaling molecules are required to activate target
- Ex: 10-8 M epinephrine
- Synaptic:
- Signal reaches selected cells
- High concentrations ofthe signaling molecules are required to activate target
- Ex: 10-4 M epinephrine
14
Q
Type of Signaling Molecules
A
- Proteins:
- PGSL-1
- Integrins (CD11/CD18)
- Peptides:
- Vasopressin
- Insulin
- TRH
- Amino Acids
- Glutamate
- Glycine
- Nucleotides
- ATP
- Adenosine
- Fatty Acid Derivatives
- Prostaglandins
- Leukotrienes
- Cholesterol Derivatives
- Aldosterone
- Progesterone
- Small molecules
- Acetylcholine
- Epinephrine
- Gasses
- Nitric Oxide
- Ions
- Ca2+
15
Q
Solubility of Signaling Molecules
A
- Solvent & Solubility
- Aqueous vs. Lipid solubility
- Ex: octanol:water partition coefficient
- Solubility and partitioning define the body space or compartment in which a signaling molecule (or drug) is distributed
- Solubility defines location of receptors that can be accessed or affected
- Carrier proteins may be used
- Aqueous vs. Lipid solubility
- Examples:
- Water Soluble
- Acetylcholine, epinephrine, glycine
- Extracellular receptors
- Lipid Soluble
- Aldoterone, Thyroid hormone
- Tyically bound to carrier proteins in plasma
- Can cross cell membrane to access cytosolic and/or nuclear receptors
- Water Soluble
16
Q
Target Molecules & Receptor Modalities
A
17
Q
Cell Surface Receptors
A
- Example:
- Vasopressin or anti-diuretic hormone (ADH)
- Signal:
- Arginine vasopressin
- Receptors:
- V1 Receptors on vascular smooth muscle cells
- V2 Receptors on Kidney collecting duct cells
- Functions:
- Increase vascular resistance and blood pressure
- Increase water retention to maintain retain vascular volume
18
Q
Cell Surface Receptors: Vasopressin
A
- Condition:
- Elevated blood osmolality and/or
- Low blood volume
- Events:
- Hypothalamic neurosecretory cells respond by releasing vasopressin in posterior pituitary, which enters vascular circulation
- V1 receptors on vascular smooth muscle cells are activated to cause releae of diacylglycerol (DAG) and IP3, which causes contraction
- V2 receptors in the nephron are actvated to increase cytosolic cAMP, which induces the insertion of aquapoins and water retention
- Outcome:
- Increased blood pressure
- Stabilize fluid volume/reduce fluid loss
19
Q
Intracellular/Nuclear Receptors
A
- Example:
- Aldosterone regulation of electrolyte concentrations
- Signal:
- Aldosterone (steroid hormone)
- Receptors:
- Mineralocorticoid (aldosterone) receptor
- Functions:
- Enhance K+ secretion and Na+ retention by kidney
- Renal collecing duct cells
- Aldosterone induces SGK1 expression
- SGK1 mdulates K+ and Na+ channel activeity and turnover
- Results in net K+ secretion along with Na+ and water retention
20
Q
Intracellular Enzymes
A
- Example:
- Nitric oxide to induce vasodilation
- Signal:
- NO
- Target:
- Guanylyl cyclase
- Functions:
- Vasodilation accompanying inflammation
21
Q
Summary
A
- Cell-to-cell signaling:
- Occurs through a variety of modalities
- Can be targeted based on
- Location of signal release
- Location of receptor
- Mechanism of distribution
- Receptor subtype
- Is concentration dependent
- Is solubility dependent
- Can be manifested over a variety of time frames
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