week 9 - cell-cell communication I

function of ECM

defines cell shape and either attaches it to another cell or acts as a first-line defense against the outside world

proteoglycans structure

consists of a core protein attached to many polysaccharides

where are ECM components synthesized?

in the rough ER, processed in the golgi apparatus, and secreted out of the cell through exocytosis

function of integrin

the intracellular portions of the integrins bind to proteins that are connected to the cytoskeleton, effectively linking the cytoskeleton and ECM

types of communication between eukaryotic cells

• communication by direct contact between cells

• indirect communication through signaling molecules

types of communication by direct contact between cells

• tight junctions

• desmosomes

• gap junctions

tight junctions structure

a tight junction is a cell–cell attachment composed of specialized proteins in the plasma membranes of adjacent animal cells. a long chain of these proteins forms on the surface of a cell that attaches to the same proteins on adjacent cells which pull the membranes of the two cells very close together this forms a watertight seal preventing solutions from flowing through the space between the two cells

where are tight junctions found?

between cells that form a barrier, such as the epithelial cells lining the stomach and intestines

tight junctions function

restrict passive movement of substances between the inside of the gut and the rest of the body

tight junctions are dynamic as they open and close in response to changes in environmental conditions, give an example of that

they loosen to permit more transport between epithelial cells lining the small intestine after a meal and then retighten later

define leaky gut syndrome

a syndrome of intestinal permeability due to disruption of tight junctions which allows for the entry of antigens into the bloodstream

desmosomes structure

• consist of integral membrane attachment proteins forming bridges between anchoring proteins inside adjacent cells

• intermediate filaments reinforce desmosomes by attaching to the anchoring proteins in the cytoplasm which forms a continuous structural support system between the cells in the tissue

desmosomes function

stop separation during contraction by joining the cells together which is important for tissues that undergo strong mechanical stress

desmosomes found in

heart and intestinal tissue

gap junction structure

gap junctions connect cells through protein channels where specialized proteins assemble in the membranes of adjacent cells, creating interconnected channels that allow water, ions, and small molecules such as amino acids, sugars, and nucleotides to move between the cells

gap junction function

work as communication portals to help adjacent cells coordinate their activities by allowing the rapid passage of regulatory ions or small molecules

define pacemaker cells

a group of specialized cardiac cells that have automatic action potential generation capability

what is the role of gap junctions in cardiac action potential?

gap junctions allow action potentials to spread between cardiac cells by permitting the passage of ions between cells, producing depolarization of the heart muscle

• therefore, all cardiac muscle cells are electrically linked together by gap junctions which allow the action potential to pass from one cell to the next

types of signals (no direct contact between cells)

• endocrine - a ligand travels through the bloodstream to reach the receptor on the target cell

• paracrine - signaling cell releases ligand to bind on the receptor on the target

• neuronal - ligand travels across the neuron to the synapse to the receptor on the target cell

• autocrine signaling - ligand released and bound on the same cell

steps of cell signaling

1- signal reception:

• a chemical signal is detected when the signaling molecule binds to a receptor protein located at the cell surface (or inside the cell)

2- signal transduction:

• the binding of the signaling molecule changes the receptor protein in some way which initiates the transduction

• the transduction stage converts the signal to a form that can result in a specific cellular response

• transduction sometimes occurs in a single step but more often requires a sequence of changes in a series of different molecules (a signal transduction pathway)

3- response:

• The cell response may be almost any imaginable cellular activity such as:

  • catalysis by an enzyme

  • rearrangement of cytoskeleton

  • activation of specific genes in the nucleus

cells in a wide array of tissues may respond to the same signaling molecule, though, if they have the appropriate receptor, example:

• if you are startled by a loud noise, cells in your adrenal glands secrete the hormone adrenaline (also called epinephrine), which carries the message “Get ready to fight or run”

• In response, your heart and breathing rates increase and cells in your liver release glucose, which your muscles can use to power rapid movement which is the basis of an “adrenaline rush”

• Cells in your heart, lung, and liver respond to adrenaline because they all have the receptor that binds to it

types of ligands and their receptors:

• hydrophobic and small molecules - interact with the receptor inside or on the surface of the cell

  • intracellular receptors

  • ligand examples: steroid hormones including sex hormones, thyroid hormones, vitamin D, and NO (induce tissue relaxation)

• hydrophilic molecules - interact with the receptor on the cell surface

  • ion channel receptors, receptor tyrosine kinase, G-protein-coupled receptors

  • ligand examples: neurotransmitters and non-steroidal hormones

define agonist

a substance that binds to a receptor and triggers the same response as the primary ligand

define antagonist

a susbstance that binds to a receptor to block or dampen the receptor’s normal response

explain the process of signal transduction of hydrophobic molecules

explain the process of signal transduction of hydrophilic molecules:

(a) ion channel receptors

explain the process of signal transduction of hydrophilic molecules:

(b) receptor tyrosine kinase (RTKs)

general mechanism:

1. one ligand binds at each binding site of the two subunits of RTK causing them to form a dimer

2. conformational change in RTK turns on catalytic activity

3. this activation allows the RTK to phosphorylate itself at tyrosine residues using ATP in the cell

4. proteins inside the cell bind to the phosphorylated RTK which initiates signal transduction

define JAK

a kinase receptor bound on the receptor

define STAT

a transcription factor

describe the JAK/STAT signaling pathway:

1. Cytokine binds to the receptor

2. Dimerization of the receptor

3. Activation of JAK and phosphorylation of the receptor

4. Phosphorylation of STAT (bound to the phosphorylated receptor)

5. Dimerization of STAT

6. Translocation of STAT dimer to the nucleus and binding to DNA

7. Activation of transcription and gene expression

describe the g-protein-coupled receptor signaling pathway:

1. signaling molecule binds to the extracellular side of the receptor

2. G-protein on the intracellular side is bound with a GDP binds to the G-protein receptor which becomes active

3. when the G-protein binds, it becomes activated by replacing GDP with GTP

4. active G-protein dissociates from the receptor and binds to an enzyme

5. when it binds to an enzyme:

   a. the enzyme becomes active and produces a secondary messenger which triggers a cell response

6. GTP is hydrolyzed to GDP and Pi which makes the G-protein inactive again

define secondary messengers:

intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules (first messengers)

what is the function of cAMP?

activates certain protein kinases

what is the function of IP3?

opens Ca2+ channels, allowing stored Ca2+ to enter the cytosol

what is the function of Ca2+?

• binds to receptor calmodulin (calcium modulating protein) which then activates kinases

• stimulates muscle contraction

what makes cAMP?

made by adenyl cyclase using ATP

where is the phosphate group attached in cAMP?

both 5’ and 3’ carbons

how is cAMP inactivated?

by phosphodiesterase which converts it to AMP

describe the role of cAMP in the epinephrine signal:

1. epinephrine (first messenger) binds to its alpha and beta receptors

2. inactive G-protein binds to the receptor and it becomes activated by replacing GDP with GTP

3. G-protein binds to adenyl cyclase which uses ATP to produce cAMP (secondary messenger)

4. cAMP binds to protein kinase A which eventually activates glycogen phosphorylase which would breakdown glycogen into glucose

describe the role of Ca2+ and IP3 in cell signaling:

1. adrenaline binds to the receptor

2. G-protein binds to the receptor and is activated by the replacing GDP with GTP

3. activated G-protein activates phospholipase C which cleaves PIP2 to DAG and IP3

4. IP3 binds to a calcium-gated channel which allows Ca2+ stored in the RER into the cytosol

5. one of the functions of Ca2+ is to cause smooth muscle contraction