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Cell-Cell Interactions

BIOLOGICAL SCIENCE
FOURTH EDITION

SCOTT FREEMAN
Lectures by Stephanie Scher Pandolfi
2011 Pearson Education, Inc.

Key Concepts
Extracellular material strengthens cells and helps bind them together.

Cell-cell connections help adjacent cells adhere. Cell-cell gaps allow adjacent cells to communicate.
Intercellular signals are responsible for creating an integrated whole from many thousands of independent parts. In target cells, intercellular signals are received, processed, responded to, and deactivated. If the signal is received at the cell surface, the processing step involves production of an intracellular signal.
2011 Pearson Education, Inc.

Review of Plasma Membrane Structure and Function


The plasma membrane is made up of a phospholipid bilayer with many interspersed proteins. Proteins may be integral or peripheral. The primary function of the plasma membrane is to create an environment inside the cell that is different from conditions outside. The selective permeability of the membrane controls the flow of materials into and out of the cell.

2011 Pearson Education, Inc.

The Structure and Function of an Extracellular Layer


Structure Most cells possess a protective layer or wall that forms just beyond the membrane. This layer generally consists of a fiber composite a cross-linked network of long filaments surrounded by a stiff ground substance. Function The rods or filaments protect against tension, and the ground substance protects against compression.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

The Primary Plant Cell Wall


When new plant cells form, they secrete a fiber composite called a primary cell wall. This wall is composed of long strands of cellulose bundled into microfibrils that form a crisscrossed network. The network is filled with hydrophilic gelatinous polysaccharides such as pectin, which keep the cell wall moist.

The primary cell wall defines the shape of the plant cell and counteracts the turgor pressure it experiences.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

The Secondary Plant Cell Wall


Some cells secrete a secondary cell wall inside the primary cell wall. Secondary cell wall structure correlates with the specific cells function. In cells that form wood, the secondary cell wall contains lignin.

2011 Pearson Education, Inc.

The Extracellular Matrix in Animals


Most animal cells secrete a fiber composite called the extracellular matrix (ECM).

Like the extracellular materials found in other organisms, one of the ECMs most important functions is structural support.
The amount and composition of the ECM vary depending upon the cell type.

2011 Pearson Education, Inc.

Extracellular Matrix Structure and Function


The ECM consists of a ground substance formed of gelatinous polysaccharide and a network of protein fibers. The most common ECM protein fiber is collagen, which is more elastic than cellulose and forms a flexible extracellular layer. In addition to structural support, the ECM also helps cells stick together, and forms protein-protein attachments that link the ECM directly to the cells cytoskeleton.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

The ECM and Cytoskeleton Are Directly Linked


The ECM is strengthened by connections to transmembrane proteins.

Actin protein filaments in the cytoskeleton bind to transmembrane integrin proteins. Integrins bind to ECM proteins such as fibronectins, which then bind to collagen. Direct linkage between the cytoskeleton and ECM keeps individual cells in place and helps adjacent cells adhere to each other. Breakdown can lead to metastasis of cancerous cells.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

How Do Adjacent Cells Connect and Communicate?


Unicellular organisms do not usually connect to one another; physical connections between cells are the basis of multicellularity. Cells of multicellular organisms adhere to one another and have specific, distinct structures and functions. Groups of similar cells performing similar functions comprise tissues.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Cell-Cell Attachments
The structures that hold cells together vary among multicellular organisms.

2011 Pearson Education, Inc.

Connections between Plant Cells


The extracellular space between adjacent plant cells comprises three layers.

Plant cells are glued together by the middle lamella, which is continuous with the adjacent plant cells primary cell walls. The middle lamella is comprised of gelatinous pectins.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Connections between Animal Cells


A middle-lamella-like layer, made of gelatinous polysaccharides, exists between cells in many animal tissues. The polysaccharide glue may be reinforced by cable-like proteins that span the ECM to connect adjacent cells. Epithelial tissue is composed of sheets of cells that cover organs and line body cavities. Many types of structures connect neighboring epithelial cells, including tight junctions and desmosomes.

2011 Pearson Education, Inc.

Tight Junctions
Tight junctions are composed of specialized proteins in the plasma membranes of adjacent animal cells. These proteins line up and bind to each other, stitching the two cells together to form a watertight seal between the two plasma membranes. Tight junctions are usually found between cells in tissues that form a barrier, such as the tissue lining the stomach or bladder. Tight junctions are dynamic and variable.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Desmosomes
Desmosomes are made of proteins that link the cytoskeletons of adjacent cells.

Desmosomes are common in epithelial and muscle tissue.


These proteins bind to each other and to the proteins that anchor cytoskeletal intermediate filaments.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Selective Adhesion
Experiments using adult sponges demonstrated selective adhesion, in which dissociated cells could aggregate and adhere to cells of the same tissue type, eventually re-forming functional adult sponges.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

The Molecular Basis of Selective Adhesion


Animal cells attach to each other selectively because there are several classes of cell adhesion proteins; each major cell type has its own cell adhesion proteins. These cell-cell connections are also species and tissue specific. Cadherins are the adhesion proteins in desmosomes.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Cell Communication via Cell-Cell Gaps


Direct connections between cells in the same tissue allow cells to communicate and work together in a coordinated fashion.

Plant cells are connected by plasmodesmata, gaps in the cell wall where the plasma membranes, cytoplasm, and smooth ER of two cells connect. In most animal tissues, gap junctions connect adjacent cells by forming channels that allow the flow of small molecules between cells.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Signaling: Direct

BLAST Animation: Signaling: Direct

2011 Pearson Education, Inc.

Summary of Eukaryotic Cell-Cell Attachments


The presence of a middle lamella, continuous ECM, tight junctions, desmosomes, and cadherins bind adjacent cells to each other. Plasmodesmata in plants and gap junctions in animals allow adjacent cells to communicate.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

How Do Distant Cells Communicate?


The activities of cells, tissues, and organs in different parts of a multicellular organism are coordinated by long-distance signals.

2011 Pearson Education, Inc.

Hormones Are Long-Distance Messengers


A hormone is an information-carrying molecule that is secreted from a cell, circulates in the body, and acts on target cells far from the signaling cell. Although hormones are usually small molecules and are typically present in minute concentrations, they have a large impact on the condition of the organism as a whole. The function and chemical structure of plant and animal hormones vary widely.

2011 Pearson Education, Inc.

Hormones Vary Widely in Effect and Structure


In addition to differences in their effects on their target proteins and chemical structure, hormones may be soluble or insoluble in lipids.

Lipid-soluble hormones usually diffuse across the plasma membrane into their target cells cytoplasm.
Lipid-insoluble hormones are large or hydrophilic and do not cross the plasma membrane but instead bind to a receptor on the cells plasma membrane.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Steps of Cell-Cell Signaling


Cell-cell signaling occurs in four steps: 1. Signal reception 2. Signal processing 3. Signal response 4. Signal deactivation

2011 Pearson Education, Inc.

Step 1: Signal Reception


Hormones and other cell-cell signals bind to signal receptors. The presence of an appropriate receptor protein dictates which cells will be able to respond to a particular hormone. Identical receptors in diverse cells and tissues allow long-distance signals to coordinate the activities of cells throughout a multicellular organism.

2011 Pearson Education, Inc.

Signal Receptors
Signal receptors are proteins that change their shape or activity after binding to a signaling molecule. Receptors are dynamic and may change in their sensitivity to particular hormones. Receptors can be blocked. Signal receptors that bind to lipid-soluble hormones are located inside the cell, but most signal receptors are located in the plasma membrane.

2011 Pearson Education, Inc.

Step 2: Signal Processing


Lipid-soluble hormones that cross the plasma membrane produce different cell responses from lipid-insoluble hormones that bind to membrane receptors.

2011 Pearson Education, Inc.

Signal Processing in Lipid-Soluble Hormones


Lipid-soluble steroid hormones bind to receptors inside the cell and trigger a change in the cells activity directly.

In this case the hormone-receptor complex is transported to the nucleus, where it alters gene expression.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Signaling via Steroid Hormones

BLAST Animation: Signaling via Steroid Hormones

2011 Pearson Education, Inc.

Signal Processing in Lipid-Insoluble Hormones


Hormones that cannot diffuse across the plasma membrane bind to membrane receptors.

When a signal binds at the cell surface it triggers a complex series of events, collectively called a signal transduction pathway, which converts the extracellular hormone signal to an intracellular signal.
The message transmitted by a hormone is amplified as it changes form. Signal transduction occurs at the plasma membrane. Amplification occurs inside.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Signal Transduction
Signal transduction involves G proteins or enzyme-linked receptors. G proteins trigger the production of an intracellular messenger. Enzyme-linked receptors trigger the activation of a series of proteins inside the cell.

2011 Pearson Education, Inc.

G Proteins
G proteins are intracellular peripheral membrane proteins that are closely associated with transmembrane signal receptors.

When G proteins are activated by a signal receptor, they trigger the production of messengers inside the cell. G proteins link the receipt of an extracellular signal to the production of an intracellular signal.
G proteins are activated when they bind GTP and are deactivated when they hydrolyze the bound GTP to GDP.

2011 Pearson Education, Inc.

G Proteins and Signal Transduction


Linking an external signal to the production of an intracellular signal involves three steps.

1. Hormone binds to the membrane receptor, which changes shape and activates G protein.
2. G protein exchanges GDP for GTP and splits into two parts. 3. One part of the G protein activates a membrane enzyme, which catalyzes the production of a second messenger.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Second Messengers
Second messengers are small molecules that diffuse rapidly throughout the cell, amplifying the hormone signal. Several second messengers work by activating protein kinases, which add a phosphate group to, or phosphorylate, other proteins.

2011 Pearson Education, Inc.

Enzyme-Linked Receptors
Enzyme-linked receptors are transmembrane proteins that bind a hormone signal and directly catalyze a reaction inside the cell.

The best-known group of enzyme-linked receptors is the receptor tyrosine kinases (RTKs).

2011 Pearson Education, Inc.

Receptor Tyrosine Kinases and Signal Transduction


Directly catalyzing an intracellular reaction involves five steps: 1. Hormone binds to an RTK. 2. RTK forms a dimer and is phosphorylated by ATP. 3. Proteins build a bridge between RTK and the Ras protein, which is subsequently activated. 4. Ras triggers the phosphorylation and activation of another protein.

5. Phosphorylation cascade, with each phosphorylated protein catalyzing the phosphorylation of other proteins, amplifies the original signal many times over.
2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

2011 Pearson Education, Inc.

Signaling Across Membranes

BLAST Animation: Signaling Across Membranes

2011 Pearson Education, Inc.

Results of Signal Processing


Many of the key signal transduction events observed in cells occur via G proteins or enzyme-linked receptors.

The signal transduction event has two results:


1. Easily transmitted extracellular message is converted into an intracellular message. 2. Original message is often amplified many times over.

2011 Pearson Education, Inc.

Step 3: Signal Response


The ultimate response to a cell-cell signal varies from signal to signal and from cell to cell, but fall into two general categories:

1. A change in which genes are being expressed in the target cell 2. Activate or deactivate a particular target protein that already exists in the cell

2011 Pearson Education, Inc.

Step 4: Signal Deactivation


Turning off cell signals is just as important as turning them on. Cells have automatic and rapid mechanisms for signal deactivation. These mechanisms allow the cell to remain sensitive to small changes in the concentration of hormones or in the number and activity of signal receptors.

2011 Pearson Education, Inc.

Summary of Hormonal Signaling


The end result of cell sensitivity to hormonal signaling is an integrated whole-organism response to changing conditions both inside and outside the multicellular organism.

2011 Pearson Education, Inc.

Interactions between Signaling Pathways


Each cell has many intracellular and membrane signal receptors, and receives an almost constant stream of different chemical signals about changes in their environment. The signal transduction pathways that are triggered by these signals and receptors intersect and connect, forming a complex network that allows cells an integrated response to an array of extracellular signals.

2011 Pearson Education, Inc.

Cross-Talk, Interactions between Signaling Pathways


Cross-talk integrates the diverse signals that a cell receives. Elements or products from one pathway may affect another pathway, ultimately affecting the overall cell response: Cell response can be reduced when one pathway inhibits another. Cell response can be increased when one pathway stimulates another. There are multiple points where the cell can regulate the flow of information, allowing the cell to respond appropriately to many simultaneous signals.

2011 Pearson Education, Inc.

Quorum Sensing in Bacteria


Even unicellular organisms live together and communicate with one another. Cell-cell communication in bacteria is called quorum sensing. Bacteria release species-specific signaling molecules when their numbers reach a specific threshold.

Response to the signal molecules varies across species.

2011 Pearson Education, Inc.

Responses to Signaling in Bacteria


Bioluminescence, or light emission Secretion of proteins that allow the bacteria to attack multicellular hosts and cause disease Production and secretion of biofilms hard, polysaccharide-rich substances that encase the cells and attach them to a surface

2011 Pearson Education, Inc.