Cell signaling

What is contact-dependent signaling

signal remains attached to cell surface receptor of the signaling cell and influences only those cells it contracts (NOT RELEASED) 

What is paracrine signaling

signals (local mediators) are released but affect only targets in the vicinity

What is synaptic signaling

nervous system neurons with long axons that release chemical neurotransmitters onto post-synaptic sites 

What is endocrine signaling

hormonal system cells synthesize and release chemical (protein, steroid, amine-derived) hormones into bloodstream to affect distant targets 

What are autocrine signals

cells produces signals that they respond to themselves 

• Cancer cells 

What are signal integration ion-channels

What are effector proteins

gene regulatory proteins, enzymes, ion channel proteins, parts of a metabolic pathway, or cytoskeletal proteins 

What is the basic principle of cellular communication

Reception of signal depends on receptor proteins on cell surface or within cell or on cell nuclear membrane  

• Binding of signal activates receptor, then signal pathway is activated 

• Intracellular signaling proteins process signals, then effector proteins target changes in cell behavior 

  • Effector proteins

What is signal integration

Signal integration = cells must integrate and respond to multiple signals to provide the appropriate action at the appropriate time 

• No signal, no receptor => cell death likely 

What are intracellular signaling proteins

once a cell membrane receptor has bound an extracellular signal, a second messenger is sent within the cell 

• Second messenger signals like cAMP and calcium or diacylglycerol pass along the signal to effectors 

  • Effectors = molecular switches (on and off properties) 

• Include GTP binding, phosphorylation via kinases, removal of phosphate by phosphatases, altered protein conformation 

  • Changes must be reversible or an over-action will occur 

What are extracellular signal molecules & the 3 different types

Extracellular signal molecules = mediate communication between cells 

Extracellular signals = membrane bound molecules or signals released into extracellular space by exocytosis or diffusion into extracellular space 

• Bind specific receptors on cell surface (transmembrane proteins) or other places in a cell 

Ex: proteins, amino acids, steroids/hormones, & nitric oxide 

 types:

1. contact dependent signaling

2. paracrine signaling

3. long range signalers

What is contact dependent signaling

Contact dependent signaling = signal remains attached to cell surface receptor of the signaling cell and influences only those cells it contacts 

• Important during development and immune response 

• Direct contact 

type of extracellular signaling

What is paracrine signaling

signals (local mediators) are released but affect only targets in the vicinity 

• Signaling cells and targets are different types of cells 

• Autocrine signals (cancer cells) 

• 1 cell releases signal, nearby cell detects 

type of extracellular signaling

What is long range signalers? describe both types

1. Synaptic = nervous system neurons with long axons that release chemical neurotransmitters onto post-synaptic sites (synapse is the locale of release) 

• These sites then have an electrical reaction (action potential) based upon the type of neurotransmitter binding to the post-synaptic receptors 

• Target cell in neurons 

2. Endocrine = hormonal system cells synthesize and release chemical (protein, steroid, amine-derived) hormones into bloodstream to affect distant targets 

• Releasing molecules into the bloodstream 

type of extracellular signaling

What are the types of responses a cell can have to a signal

Cellular response = different cell types respond to the same signal differently 

• Dependent on internal signals, effectors, and genes 

  Ex responses:  

• Decreased firing rate 

• Secretion 

• Muscle contraction 

Response to extracellular signal = can be fast or slow, depends on mechanism of delivery, nature of response and turnover of signals 

• Fast response = if changes occur to proteins already present within cell (less than a sec. to mins) 

  • altered protein function 

• Slow response = if changes to gene expression or new protein synthesis are required (mins to hrs.) 

  • altered protein synthesis 

What are the 3 classes of cell-surface receptors

1. ion-channel coupled

2. GPCR

3. Enzyme coupled receptors

What is Ion-channel coupled receptors (ionotropic/transmitter-gated)

Ion-channel coupled (ionotropic/transmitter-gated) = rapid signals mediated by neurotransmitters that open or close ion channels based on excitation or inhibition of the post-synaptic target 

• Transmit signal fast 

Ex: ion channel is coupled to a transmembrane protein 

What are G-protein-coupled receptors (GPCR)

G-protein-coupled receptors (GPCR) = signal activates receptor and GTP-binding protein (G-protein) which in turn activates the target 

• Targets can be enzymes, other proteins, ion channels 

• G-protein subunit attaches to cytosolic lipid bilayer with an anchor 

What are enzyme-coupled receptors

Enzyme-coupled receptors = can act as enzymes themselves once activated or associate and activate with enzymes intracellularly 

What is a second messenger system

Delayed response to steroid hormone 

• One of the ways to respond to hormones 

  2 step process 

• A primary response protein shuts-off primary response gene 

• A primary response protein turns on secondary-response genes 

What are types of cellular responses

second messenger systems

phosphorylation

extracellular signal responses;

What is phosphorylation

Reaction in which a phosphate group is covalently coupled to another molecule 

What are nuclear receptors

Nuclear receptors = hydrophobic signal molecules that move directly across the cell membrane and bind to intracellular receptor proteins (which then control transcription) 

• Steroid hormones, fat soluble vitamins, thyroid hormones 

• Belong to a superfamily 

• Transcriptional responses takes multiple steps 

What are GPCR proteins

used by all eukaryotes (largest family of cell surface receptors) 

• Broad variety of function in sensation, neurotransmission, endocrine system, cell communication, drug and external world signaling 

• All GPCRs have a similar structure: polypeptide with several transmembrane domains and all use G proteins to signal cell interior 

What are G proteins & their structure

trimeric GTP-binding proteins attached to cytoplasmic (inside the cell) face of cell membrane  

• Couples the receptor to either enzymes or ion channels 

• When signal binds to GPCR, the receptor activates the G protein 

• G proteins are specific for sets of GPCRs and a particular set of target proteins 

• Bind targets when activated that include enzymes or ion channels (activated of enzymes) 

• Considered to be stimulatory or inhibitory based on the activation of adenylyl cyclase (increases cAMP) or inhibition (decreases cAMP) of it 

  • Adenylyl cyclase synthesizes cAMP which is how some extracellular signals work to mediate a cellular response 

    • cAMP controls thyroid hormones, bone resorption, glycogen breakdown, & cortisol secretion 

Structure = composed of 3 subunits: α, β, & y 

• α (a GTPase) binds GDP and keeps G protein inactive but then releases GDP and binds GTP which activates G protein 

How does G protein activation work

Structure = composed of 3 subunits: α, β, & y 

• α (a GTPase) binds GDP and keeps G protein inactive but then releases GDP and binds GTP which activates G protein 

What are common causes in cell communication that lead to disease

Signals are lost

• Diabetes type 1

• Loss of immune protection

Cell signal does not reach target

• Multiple sclerosis

Target cell does not respond

• Diabetes type 2

Too much signal

• Stroke with release of glutamate in brain

How does cell communication errors lead to cancer

Cancer = cell growth and division continues despite the absence of signal and loss of self-destruction, allowing for new signals to promote angiogenesis 

• Dysregulation of leukocyte adhesion and endothelial cell interaction contribute to the cancer (and vascular occlusion in sickle cell/sepsis)