PSYC 427 - Intracellular Signaling

What are gap junctions (animal)/plasmodesmata (plants)?

Like “doors” for cells to directly exchange materials between the cytoplasm and communicate

What does paracrine mean?

The release of a chemical signal from one cell that is detected by and alters the function of a closely related cell

What does autocrine mean?

The release of a chemical signal from one cell that is detected by and alters the function of the same cell

What is the difference between autocrine, paracrine, and synaptic signaling versus endocrine signaling?

Endocrine signaling occurs over long distances

What types of molecule act as signals?

Amino acids and their derivatives, steroids, peptides and proteins

What do soluble molecules do in cell-cell signaling?

They tend to act as receptors on the surface of target cells

What do insoluble molecules do in cell-cell signaling?

These pass thru cell membranes and act as receptors inside the target cells

What do phytoestrogens do?

They can go in cells (insoluble) and turn genes on (don’t need a receptor on the cell surface)

What are the three stages to the signaling process in the target cell?

Reception, transduction, and response

What is the purpose of transduction?

To alter enzyme function or gene expression

What are the advantages of signal transduction?

1) Allows the signal to be amplified

2) Allows one signal to diverge and control a range of cellular processes

3) Allows other signals to control the cascade

What are some characteristics of second messengers?

1) Trigger the transduction cascade

2)Their intracellular concentrations are controlled by receptor activation

3) They function as intermediaries between the receptor and the cascade

4) Three principal second messengers (cAMP, Ca2+, IP3)

What is fast signaling due to?

Changes in preexisting protein function

What are slow responses due to?

Changes in the rate or type of protein synthesis (requires changes in gene transcription or translation)

What is a kinase?

An enzyme that adds a phosphate group onto another molecule (protein) and often another enzyme

What does the phosphate group do?

It changes the conformation of the protein and alters its function

What does phosphatase do?

Removes phosphate groups

What are the three classes of cell surface receptor proteins?

1) Ion channel coupled receptors (ionotropic)

2) G protein coupled receptors (metabotropic)

3) Enzyme coupled receptors (adenylyl cyclase)

What do ion channel coupled receptors do?

Bind NT and change the ion permeability of the plasma membrane

What are the ‘actors’ involved with g protein coupled receptors?

1) inactive transmembrane receptor (traverses the membrane multiple times)

2) G protein

3) another transmembrane protein (enzyme)

How do G protein coupled receptors work?

1) When a NT binds to the receptor, the receptor binds the G protein

2) G protein replaces GDP with a GTP and becomes activated

3) The activated G protein shuttles over to activate the enzyme, leading to a cellular response

4) After the ligand unbinds from the receptor, the response is terminated; G protein cuts off the phosphate so that GTP turns back to GTP to GDP) (converts GDP t and slides back to the receptor

What is the signaling pathway of G proteins?

1) First messenger (signaling molecule) activates G protein coupled receptor which sends G protein to bind with adenylyl cyclase

2) Adenylyl cyclase catalyzes a cyclization reaction that removes two phosphates from ATP and forms cAMP (second messenger)

3) cAMP activates inactive protein kinases which forms the phosphorylation cascade leading to the activation of a protein (cellular response)

4) This can be terminated by cAMP phosphodiesterase hydrolyzing cAMP into 5’-AMP; unbinding the signaling molecule; or converting GTP to GDP done by the G protein

What can ATP be turned into?

cAMP, done with the help of adenylyl cyclase

What happens during the response?

1) The phosphorylation cascade activates the inactive transcription factor with a phosphate

2) This sits on the DNA to turn on a gene to be transcribed into mRNA

3) After transcription comes translation in which a protein is made

What is different between ionotropic receptors and G coupled receptors?

G coupled receptors allow for the process of axonal growth

How can Ca2+ and IP3 be involved in signaling pathways?

1) Once the G protein is activated, it activates phospholipase C leading to the formation of IP3 from PIP2

2) IP3 (Second messenger) binds to a Ca2+ channel in the ER and leads to the release of Ca2+ (second messenger)

3) This activates various proteins and leads to cellular responses

What is the ER lumen considered as?

A Ca2+ storage unit

How is Ca2+ signaling terminated?

It is removed from the cytoplasm by Ca2+ pumps which move Ca2+ against the concentration gradient (Active transport); pumped out the cell, into the mitochondria, or into the smooth ER

What are characteristics of enzyme coupled receptors?

1) Transmembrane proteins that have their ligand binding domain on the extracellular face and their catalytic site on the intracellular face

2) Are almost all protein kinases: proteins that phosphorylate other proteins

3) Exist as a pair of monomers which come together when ligands bind onto the receptors (gives the receptors the ability to pick up phophates)

What are some characteristics of receptor tyrosine kinases?

1) common type of enzyme coupled receptor

2) Bottom portion is made up of kinases and tyrosine groups

3) Made up of an extracellularly facing ligand binding site, an alpha helix spanning the membrane, and an intracellular tail with multiple tyrosines

How are enzyme coupled receptors activated?

1) Signaling molecules bind to both monomers which dimerizes them

2) The kinase regions of the two monomers phosphorylate, in which the two monomers phosphorylate each other at the tyrosines and activates the proteins (done with atp)

3) once activated, inactive relay proteins are drown to the phosphorylated tyrosines and bind to them, triggering a cellular repsonse

What kind of receptors are insulin receptors?

Enzyme coupled receptor

How do insulin receptors work?

One output of signal transduction of the insulin receptors is bringing in glucose (comes in thru GLUT4 which is put into the cell membrane)

Why does the neuron not need insulin receptors?

They have glucose receptors already on the surface