Chapter 11

Cell Communication

 

Objectives:

 

(i) Know how yeast cells communicate.

 

(ii) Know local versus long-distance signaling and their examples.

 

(iii) Know three stages of signaling.

 

(iv) Intracellular versus plasma membrane receptors.

 

(v) know the phosphorylation cascade

 

(vi) Know small molecules and second messengers.

 

(vii)  Know cellular response –

 

(viii) Know that fine-tuning of the response includes amplification and specificity of signaling.

 

 

 

 

 

 

Overview: The Cellular Internet

 

•Cell-to-cell communication is essential for multicellular organisms

•Biologists have discovered some universal mechanisms of cellular regulation

 

In Cell communication, external signals are converted into responses within the cell

 

•Microbes are a window on the role of cell signaling in the evolution of life

 

Evolution of Cell Signaling

 

•A signal-transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response

•Signal transduction pathways convert signals on a cell’s surface into cellular responses

•Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and have since been adopted by eukaryotes

 

Fig. 11-2 shows the signaling in Saccharomyces cerevisiae. It shows that the yeast cells a and α cells secrete factor and factor α, respectively.  A cell has receptors that recognize α factor and α cell has receptors that recognize the factor α.  Recognition of factors secreted by the other mate induces changes that lead to their binding and nuclear fusion. 

 

Local and Long-Distance Signaling

 

•The cells in a multicellular organisms communicate by chemical messengers.

 

•Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells and communicate via exchange of ions.   Some cells may communicate by direct contact between membrane-bound receptors.(Fig.11-3).

 

•In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances.  In long-distance signaling, plants and animals use chemicals called hormones.  Local signaling is shown in Fig. 11.4 a.  The figure shows that a secreting cell secretes molecules that are recognized by the receptors of some cells in the near vicinity.   The cells that recognize the secreted molecules are called target cells  Fig. 11-4

 

The other example of  local signaling is the signaling between a nerve terminal and the target cell.  Here the neurotransmitter released by the nerve cell stimulates the target cell.  The target cell may be a gland, muscle or other nerve cell.

 

The Three Stages of Cell Signaling: A Preview (Fig. 11.5)

•Earl W. Sutherland discovered how the hormone epinephrine acts on cells

•Sutherland suggested that cells receiving signals went through three processes:

 

(i) Reception – Detection of signal molecule by the receptor of a cell.  The receptor protein may be inside the cell or embedded in the plasma membrane.

 

(ii) Transduction – Binding of  signal to the receptor protein converts signal to a series of reactions.   

 

(iii) Response – the transduced signal (i.e. the sequence of chemical reactions within the cell) leads to a cellular response.  This response may be any response.  Some examples are the contraction of a muscle, secretion of hormones by the gland or activation of an enzyme.

 

 

 Reception: A signal molecule binds to a receptor protein, causing it to change shape

•The binding between a signal molecule (ligand) and receptor is highly specific

•A conformational change in a receptor is often the initial transduction of the signal

•Most signal receptors are plasma membrane proteins

 

Intracellular Receptors

•Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells

•Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors

•Examples of hydrophobic messengers are the steroid and thyroid hormones of animals

•An activated hormone-receptor complex can act as a transcription factor, turning on specific genes

(Fig 11-6)

 

Receptors in the Plasma Membrane

•Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane

• 

•There are three main types of membrane receptors:

–G-protein-linked receptors

–Receptor tyrosine kinases

–Ion channel receptors

 

•A G-protein-linked receptor is a plasma membrane receptor that works with the help of a G protein

•The G-protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive

(Fig 11-7aa)

 

•Receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines

•A receptor tyrosine kinase can trigger multiple signal transduction pathways at once

(Fig 11-7b)

 

•An ion channel receptor acts as a gate when the receptor changes shape

•When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

(Fig. 11-7c)

 

Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell

 

•Transduction usually involves multiple steps

•Multistep pathways can amplify a signal: A few molecules can produce a large cellular response

•Multistep pathways provide more opportunities for coordination and regulation

 

Signal Transduction Pathways

 

•The molecules that relay a signal from receptor to response are mostly proteins

•Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated

•At each step, the signal is transduced into a different form, usually a conformational change

 

Protein Phosphorylation and Dephosphorylation

 

•In many pathways, the signal is transmitted by a cascade of protein phosphorylations

•Phosphatase enzymes remove the phosphates

•This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off

(Fig 11-8)

 

Small Molecules and Ions as Second Messengers

 

•Second messengers are small, nonprotein, water-soluble molecules or ions

•The extracellular signal molecule that binds to the membrane is a pathway’s “first messenger”

•Second messengers can readily spread throughout cells by diffusion

•Second messengers participate in pathways initiated by G-protein-linked receptors and receptor tyrosine kinases

 

Cyclic AMP

•Cyclic AMP (cAMP) is one of the most widely used second messengers

•Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal

Fig. 11-9

 

•Many signal molecules trigger formation of cAMP

•Other components of cAMP pathways are G proteins, G-protein-linked receptors, and protein kinases

•cAMP usually activates protein kinase A, which phosphorylates various other proteins

•Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase

Fig. 11-10

 

Calcium ions and Inositol Triphosphate (IP3)

• 

•Calcium ions (Ca2+) act as a second messenger in many pathways

•Calcium is an important second messenger because cells can regulate its concentration

Fig. 11-11

 

•A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol

•Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as second messengers

 

Fig. 11-12_1 to 3

 

Response: Cell signaling leads to regulation of cytoplasmic activities or transcription

 

•The cell’s response to an extracellular signal is sometimes called the “output response”

 

Cytoplasmic and Nuclear Responses

 

•Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities

•The response may occur in the cytoplasm or may involve action in the nucleus

•Many pathways regulate the activity of enzymes

Fig. 11-13

 

•Many other signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus

•The final activated molecule may function as a transcription factor

 

Fig. 11-14

 

Fine-Tuning of the Response

• 

•Multistep pathways have two important benefits:

–Amplifying the signal (and thus the response)

–Contributing to the specificity of the response

 

Signal Amplification

•Enzyme cascades amplify the cell’s response

•At each step, the number of activated products is much greater than in the preceding step

 

The Specificity of Cell Signaling

 

•Different kinds of cells have different collections of proteins

•These differences in proteins give each kind of cell specificity in detecting and responding to signals

•The response of a cell to a signal depends on the cell’s particular collection of proteins

•Pathway branching and “cross-talk” further help the cell coordinate incoming signals

Fig. 11-15

 

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes

 

•Scaffolding proteins are large relay proteins to which other relay proteins are attached

•Scaffolding proteins can increase the signal transduction efficiency

Fig. 11-16

 

Termination of the Signal

 

•Inactivation mechanisms are an essential aspect of cell signaling

•When signal molecules leave the receptor, the receptor reverts to its inactive state