Exam 3 Kaja 1: Cell Signaling 1

Question 1

An extracellular signaling molecule is called a “___”

They bind to _____ on the surface of the plasma membrane, illiciting a intracellular signaling cascade

Answer 1

Extracellular signaling molecule is a “ligand”

Ligands bind to receptor proteins that span the plasma membrane and illicit an intracellular response

Question 2

A _______ is a signaling triggering molecule, binding to a site on a target protein via:

• Ionic Bonds
• Hydrogen Bonds
• van der Waals forces

The docking is usually _______ (one exception?)

Answer 2

LIGAND is a signaling triggering molecule, binding to a site on a target protein via:

• Ionic Bonds
• Hydrogen Bonds
• van der Waals forces

Docking is usually reversible (except for neurotoxins)

Question 3

Ligand binding to a receptor protein ___________

The conformational state of a receptor protein determines its _______

Ligands include: ___, ____, ____, ____

Strength of binding is called______

Answer 3

Ligand binding to a receptor protein alters its chemical conformation

The conformational state of a receptor protein determines its functional state (shape—> function)

Ligands: substrates, inhibitors, activators, and NTs

Strength of binding is affinty

Question 4

A ______ is a molecule found on the surgace of a cell, which receives specific chemical signals either from intra cells or inter cells - the wider enviornment within an organism such as the circulatory system

Answer 4

RECEPTOR

Question 5

A lot of times the signal molecule is ______

Answer 5

A lot of times the signal molecule is hydrophobic because the plasma membrane is hydrophobic

Question 6

What are the four forms of intercellular signaling?

Answer 6

Four forms of intercellular signaling:

1. Contact-Dependent
2. Paracrine
3. Synaptic
4. Endocrine

“Everyday signal is Crappy and poor”

Question 7

Describe contact dependent signaling

Answer 7

Contact dependent signaling:

A type of intracellular communication whereby a signal molecule reamains bound to the signaling cell surface and influences only cells that come into contact with it.

Question 8

Explain paracrine signaling

Answer 8

Paracrine: “para” means close by

Paracrine signals are signals that are released into extracellular space and act locally on neighboring cells

Examples: TGF and FGF

Question 9

Explain autocrine signaling

Answer 9

Autocrine: cells secrete substances that influence themselves

often related to feedback mechanisms

Question 10

Explain endocrine signaling

Answer 10

Endocrine signaling depends on endocrine cells, which secrete hormones into the bloodstream that are then distributed widely throughout the body

Question 11

Most hormones travel around the body via the ____

Answer 11

Hormones travel in the bloodstream

Question 12

Neurons transmit signals electrically along their axons and release NTs at _______, which are often located far away from the cell body

Answer 12

Neurons transmit signals electrically along their axons and release NTs at synapses, which are often located far away from the cell body.

Question 13

A ______ is a structure that permits a neuron to pass an electrical or chemical signal to another cell

At that structure, the plasma membrane of the signal passing neuron ________ with the membrane of the target cell

Answer 13

A synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell

At that structure the plasma membrane of the first neuron comes into close proximity with the membrane of the target cell

Question 14

Explain gap junctions:

Definition

Diameter

What do they permit?

Answer 14

Gap Junctions: narrow water filled channels that directly connect the cytoplasm of adjacent cells

Diameter is 1.5 - 2.0 nm

GJs permit the free passage of ions and small molecules between cells

Question 15

Gap junctions are cylinders constructed from ___ copies of transmembrane proteins called _____

(Example in cardiac cells, APs in the heart flows from cell to cell via gap junctions)

Answer 15

GJs are cylinders constructed from 6 copies of transmembrane proteins called connexins.

Question 16

ACh is released from the _____ nerve.

It was also the ____ NT to ever be discovered.

It functions in both the ____ and the ______

In the PNS: ACh activates/deactivates skeletal muscle…… ACh activates/deactivates cardiac

The CNS ACh associated system is called ___

Answer 16

ACh is released from the vagus nerve

It was first NT to ever be discovered

It functions in BOTH the PNS and the CNS

In the PNS: ACh activates skeletal muscle, inactivates cardiac muscle

CNS ACh system is the “cholinergic system”

Question 17

Damage to the ______ system in the brain is related to Alzhiemer’s Disease

Answer 17

Alzhiemer’s Disease: damaged cholinergic system

Question 18

The disease ________ characterized by muscle weakness and fatigue, occurs when the body inappropriatedly produces antibodies against ACh nicotonic receptors, and thus inhibits proper ACh signal transmission

Answer 18

myasthenia gravis : body produces antibodies against ACh nicotonic receptors… muscle weakness and fatigue

Question 19

A _____ is a substance governing the pattern of tissue development, and the positions of the various specialized cell types within a tissue

It spreads from _____ source

Answer 19

A morphogen is a substance governing the pattern of tissue development, and the positions of the various specialized cell types within a tissue

It spreads from a localized source and forms a concentration gradient across a developing tissue

Question 20

Where is rapid turnover utilized in medicine

Answer 20

Rapid turnover means small half life

Half life is used in pharmocology

Question 21

________ which has been used to treat angina, it causes vasodialation and relaxes blood vessels

Explain the mechanism

Answer 21

Nitroglycerin which has been used for about 100 years to treat angina (pain resulting from inadequate blood flow to the heart muscle)

Mechanism:

ACh binds to NOS, an enzyme which converts arginine to NO, which then activates guanalyl cylase (converts GTP to cyclic GMP), and the cyclic GMP is what causes rapid relaxation of smooth muscle cell

Question 22

Sidenifil/ viagra involves the protection of ______ from degradation by inhibiting the enzyme _______, promoting vasodialation

Answer 22

Sidenifil/Viagra protects cGMP (a vasodialator) from degradation by inhibiting the enzyme cGMP-PDE5

Question 23

Give some examples of some signaling molecules that bind to nuclear receptors

Answer 23

Steroid hormones, thyroid hormones, retinoids, vitamin D all cross plasma membrane

Question 24

Nuclear receptor superfamily:

What do the nuclear receptor superfamily all share in common?

Big major difference

Answer 24

Nuclear receptor superfamily share a DNA binding domain and also the homology of the C terminal .

The ligand binding domain in on the C terminus

Question 25

Once a ligand binds to a nuclear receptor, what two things happen?

Answer 25

Ligand binds to nuclear receptor and causes:

1. conformational change
2. causes the receptor to bind to coactivator proteins that induce gene tx

Question 26

Explain primary/early response to steroid hormones

vs

Secondary/delayed response to steroid hormones

Answer 26

Primary/Early response: steroid hormone binds to steroid receptor and activates primary response genes, those primary reponse proteins can then act quickly

Secondary/Delayed Response: when primary response proteins are involved in feedback mechanism that activate other gene tx called secondary response

Question 27

Name the three largest classes of cell-surface receptor proteins

Answer 27

Cell surface receptor proteins:

Ion Channel-linked receptors

G-protein linked receptors

Enzyme linked receptors

Question 28

Ion channel receptor are involved in _______ between electrically excitable cells

This signaling is mediated by ______ that ___

Answer 28

Ion channel receptors are involved in rapid synaptic signaling between electrically excitable cells

Signaling is mediated by a small number of NTS that open or close an ion channel to which they bind to

Question 29

G protein coupled receptors act _______ to regulate the activity of a second plasma membrane bound target protein

The interaction between receptor and target proteins is mediated by ____ called a _______

Answer 29

G protein coupled receptors act indirectly to regulate the activity of a seperate protein, which can be an ion channel or enzyme

The interaction between the receptor and this target protein is mediated by a third protein, called a trimeric GTP-binding protein

Question 30

Enzyme linked receptors are ______ in structure compared to the other two classes

The great majority of them are protein kinases, and ligand binding to them causes ______ of specific proteins in the target cell

Answer 30

Enzyme linked receptors are heterogenous in structure compared to the other two classes

The great majority of them are protein kinases, and ligand binding to them causes phosphorylation of specific target proteins in the cell

Question 31

What are the two types of intracellular signaling proteins that act as molecular switches

Answer 31

Signaling by phosphorylation

Signaling by GTP-binding

Question 32

What kind of signaling acts like a molecular clock

Answer 32

GTP

Question 33

What are the three types of intracellular signaling complexes?

Answer 33

Intracellular signaling complexes

1. scaffold protein
2. “activated receptor”
3. phosphoinositide docking sites

Question 34

Explain the mechanism of preformed signaling complex on a scaffold protein

Answer 34

A receptor and some of the intracellular signaling proteins it activates in sequence are preassembled into a signaling complex on the inactive receptor by a large scaffold protein.

Scaffold proteins hold things together in close proximity

Question 35

Explain how intracellular signaling works with an “activated receptor”

Answer 35

Activated receptor:

First, an extracellular singal binds to a receptor and activates it

The activated receptor phosphorylates itself at multiple sites, which acts as docking sites for intracellular signaling proteins

Question 36

Explain the intracellular signaling mechanism associated with phosphoinositide docking sites

Answer 36

Activation of a receptor leads to increased phosphorylation of specific phospholipids in the adjacent plasma membrane (called “phosphoinocitides”)

These extra phosphorylated sites act as docking sites for specific intracellular signaling proteins

Question 37

Explain the insulin receptor

(Draw it out and talk it out)

Answer 37

Question 38

What are the five ways in which target cells can become desensitized to a signal molecule?

Answer 38

Five ways in which target cells can become desensitized to signal molecule:

1. Receptor sequestration into endosome
2. Receptor Down regulation
3. Receptor Inactivation
4. Inactivation of signaling protein
5. Production of Inhibitory Protein