Cell Bio Exam 4

Every cell has a specific set of receptors and responses

a cell can only respond to a signal that it has a receptor for

the same signal/receptor interaction in different cells can have very different responses

• determined by which proteins are being triggered by the relay molecules

Cells require the input of several signals

A single signal alone is not enough to shape the behavior of a cell

Multiple different signals must be coordinated to achieve the desired result

Several signals are required for survival, while additional signals can trigger growth, development, or taking on a new fate

cells react to signals at different rates

responses that occur in the cytosol (release of vesicles, phosphorylation of enzymes) take seconds to minutes

Responses that require changes in gene expression (growth, division, differentiation) can take up to hours to cause changes

Stages of signal transduction

reception, transduction, and response

Intracellular relay signaling molecules work in many different ways

1. Each molecule can simply relay the signal forward to the next signaling molecule in a linear fashion

2. Can amplify the received signal

• Often achieved using secondary messengers

• small molecules like cAMP or Ca²⁺ that are spread around easily and quickly, and many different proteins respond to

3. Can detect and integrate multiple signals to relay a single signal forward

4. Can distribute the signal to 1 or more effector proteins that aid in the final response

secondary messengers

small signaling molecules

Molecular switches

proteins that are able to be quickly activated or inactivated by a signal

when activated they stay activated until another signal comes in to inactivate

Two main classes of molecular switches

add or remove phosphate groups

GTP-binding proteins - toggle back and forth between having GTP or GDP bound

Molecular switches that add or remove phosphate groups

kinases add, phosphatases remove phosphate groups

proteins can be activated or inactivated by phosphorylation

kinases are specific to which AA they can add phosphates to

• serine/threonine kinases only phosphorylate on Ser or Thr

• tyrosine kinases only phosphorylate on Tyr

GTP-binding proteins

have inherent GTPase activity (hydrolyze GTP)

activated by GTP binding, inactivated after GTP - > GDP

2 types - heterotrimeric G-protein complexes and monomeric GTPases

GTPases

Proteins that change conformation based on whether they have GTP or GDP bound

GTP-bound - typically on

GDP-bound - typically off

GEF/GAP/GTPase rules

GEFs/GAPs will always be the step before a GTPase

GEFs —> GTPase

GAPs - -| GTPase

why do single celled organisms need to communicate

respond to the environment

defense

track down food and nutrients

mating

quorum sensing

why do multi-cellular organisms need to communicate

have to be able to do everything a single celled organism does, must be coordinate with all the other cells

coordinate development

behavior

Cell signaling

cell communication is achieved by sending out signals that are converted into different forms

signal transduction

process or perceiving and converting signals into responses

Response

signal transduction begins when an extracellular signal is detected by a target cell

• signals can range from proteins, lipids, and sugars to gases, light, or gravity

• the signal can be initiated by a signaling cell, or it can be something from the environment

Target cells contain receptor proteins that recognize and respond specifically to the signal

Transduction

signal perception causes a conformational change in the receptor

triggers a cascade of reactions in which the signal is transferred among several relay molecules (ions, nucleotides, and proteins)

Response

change in behavior of a cell is a direct result of the signal

can occur through changes in gene expression, enzyme activation/deactivation, cytoskeletal rearrangement, and many more

endocrine signaling

specialized cells generate and secrete large amounts of signaling molecules that are broadcast throughout the body

in animals, signals move in the bloodstream; in plants they move in the xylem and phloem

hormone

signal of the endocrine signaling

Paracrine signaling

signals sent from one cell diffuse into the extracellular space, rather than enter a vascular pathway

includes local mediators and autocrine cell signaling

local mediators

localized signals that only act on cells near their origin

autocrine cells

percieve signals that they create themselves

contact dependent signaling

signal molecules are bound to the membrane of the signal cell, while the receptor is in the membrane of a neighboring cell

Important for developmental patterning

G-protein coupled receptors (GPCRs)

largest family of cell surface receptors

bind very diverse types of signals

general structure in all GPCRs is the same

• single polypeptide chain that contains 7 transmembrane domains

G-proteins prior to reception

inactive

alpha is bound to GDP, alpha, beta, and gamma are associated together in a complex

alpha and gamma are each tethered to the PM through lipid linkages

beta is at the PM through protein-protein interactions with a and b

G-protein after reception

transduction starts

the activated receptor recruits the G-protein, activating alpha by promoting exchange of GDP for GTP

alpha separates from beta gamma (both alpha and beta gamma are considered active and can trigger different relay steps)

alpha will hydrolyze GTP ending its ability to relay and will recruit beta gamma back into the inactive complex

the process will repeat when another signal activates the receptor

many G-proteins regulate ion channels

beta gamma will trigger opening of ion channels until GTP is cleaved by the alpha subunit

• can open K⁺, Ca⁺, Na⁺, and Cl^- ion channels

cholera toxin prevents alpha from hydrolyzing GTP

many G-proteins activate secondary messenger signaling

the two most common targets for G-proteins

• adenylyl cyclase

• phospholipase C

both enzymes function to generate secondary messengers

adenylyl cyclase (AC)

catalyzes the reaction that converts ATP to cAMP

usually activates by alpha (but not always)

will promote AC until GTP is hydrolyzed

cAMP

degraded by cyclic AMP phosphodiesterase, which is always active in a cell

one common target is protein kinase A (PKA)

cAMP activates PKA

PKA phosphorylates many different targets, including lots of transcriptional regulators in the nucleus

phospholipase C triggers Ca²⁺ signaling

activated G-proteins can trigger phospholipase C, which functions to cleave lipids in the membrane

specifically cleaves inositol phospholipids that are present only on the cytosolic side of the lipid bilayer

generates 2 second messengers

IP₃ opens ligand-gated Ca²⁺ channels in the ER, releasing Ca²⁺ into the cytosol

CaM binds Ca²⁺ the protein undergoes a conformational change, allowing it to interact with many other targets that have CaM binding sites

another common target for CaM are CaM kinases

Protein kinase C (PKC) is partly activated by Ca²⁺ and has many downstream targets similar to PKA

two secondary messengers of phospholipase C

inositol triphosphate (IP₃) and diaglycerol (DAG)

Calmodulin (CaM)

most common calcium binding proteins present in the cytosol of all eukaryotes

CaM kinases

common target for CaM that is activated by binding to CaM/Ca²⁺ complexes, and can go on to activate a variety of cellular processes

Protein kinase C (PKC)

requires interaction with DAG (at the membrane) to become fully active