Interactions between cells and their environment

integrin activation

1. switch in conformation to an inactive integrin molecule to an active form is triggered by the binding of a protein, in this case talin, to the small cytoplasmic domain of the B subunit. -Binding of talin induces a separation of the two subunits and conversion to the active conformation -activated integrins typically become clustered as a result of interactions of their cytoplasmic domains with the underlying cytoskeleton.

structural features of collagen

1. all are trimers- consisting of three polypeptide chains, called a chains 2. along at least part of their length, the three polypeptide chains of a collagen molecule are wound around each other to form a unique, rod-like triple helix

functions of proteoglycans

1. form hydrated cushions 2. serve as filter 3. bind signaling molecules 4. regulate cell migration

GAG's

_______ highly acidic due to presence of both sulfate and carboxyl groups attached to the sugar rings

cytoplasmic domains

many integrins, can exist on the surface of a cell in an inactive conformation. -these integrins can be activated rapidly by events within the cell that alter the conformation of the ___________ of the integrins subunits -changes in conformation of of ________ are propagated through the molecule, increasing the integrins affinity for an extracellular ligand. Example: the aggregation of platelets during blood clotting

proline

the a chains of collagen molecules contain large amounts of _____, and many of the _______ (and lysine) residues are hydroxylated following synthesis of the polypeptide.

matrix metalloproteinases (MMPs)

the degradation of extracellular materials, along with cell-surface proteins is accomplished by a family of zinc-containing enzymes called _________ -thought to be involved in tissue remodeling, embryonic cell migration, wound healing, and formation of blood vessels.

triple helix

the hydroxylated amino acids are important in maintaining the stability of the _________ by forming hydrogen bonds between component chains. -failure to hydroxylate collagen chains has serious consequences for the structure and function of connective tissues. -disease: scurvy

embryonic development

the importance of fibronectin and other extracellular proteins is evident during _____________ -characterized by waves of cell migration during which different cells follow different routes from one part of the embryo to another

glycocalyx

*sugar coating of cells -formed by oligosaccharides attached to proteins and lipids of plasma membrane -contains additional secreted materials that remain close to cell surface Functions: -mediate cell-cell and cell-substratum interactions -provide mechanical protection to cells -serve as a barrier to particles moving toward the plasma membrane -bind important regulatory factors that act on the cell surface **very prominent in epithelial cells that line the mammalian digestive tract

collagen

-family of fibrous glycoproteins that are present only in extracellular matrices -high tensile strength = resistance to pulling forces -single most abundant protein in the human body -produced by fibroblasts- the cells found in various types of connective tissues, and also by smooth muscle cells and epithelial cells *at least 19 different types- each type is restricted to particular locations within the body, but two or more different types are often present together in the ECM

immunoglobins

-Ig domains -composed of 70 to 110 amino acids organized into a tightly folded structure *most abundant domain in human protein -involved in various aspects of immune function -mediate calcium-independent cell-cell adhesion -VCAM, NCAM, and L1 mediate adhesion between non-immune cells

fibrillar collagens (1, 2, 3)

-assemble into rigid, cable-like fibrils, which in turn become packaged into thicker fibers -the fibrils are strengthened by covalent cross-links between lysine and hydroxylysine residues on adjacent collagen molecules ** this cross-linking process continues through life and may contribute to the decrease elasticity of skin and increased brittleness of bones among the elderly. -great mechanical strength-- staggered arrangement of molecules in fiber -provide the insoluble framework that determines many of the mechanical properties of tissues

adherens junction

-commonly found in the epithelia; such as lining of the intestine where they occur as belts that encircle each of the cells near its apical surface biding that cell to its neighboring cells -the cells are held together by by calcium-dependent linkages formed between the extracellular domains of cadherin molecules that bridge the 30 nm gap between neighboring cells -the cytoplasmic domains of cadherins is liked by a- and B-cantenins

proteoglycans

-consists of a core protein molecule to which chains of glycosaminoglycans (GAGs) are covalently attached -each glycosaminoglycan chain is composed of repeating disaccharide; that is the repeating structure A-B-A-B- = A and B represent two different sugars ** sulfate usually attached to one of two sugars -may be assembled into gigantic complexes by linkage of their core proteins to a molecule of hylauronic acid, a nonsulfated GAG ** because of the negative charges borne on the sulfated GAG's, proteoglycans bind huge numbers of cations, which in turn bind large numbers of water molecules **cushioning material and resists crushing (cushioning) forces

non fibrillar collagen (4)

-distribution restricted to basement membrane -organized into a network that provides mechanical support and serves as a lattice for the deposition of other extracellular materials-- rather than a cable -contains nonhelical segments (flexible) interspersed along the molecule and globular domains at each end (serve as sites of interaction between molecules that give the complex its lattice like character.

fibronectin

-each polypeptide is constructed from a sequence of 30 independently folding Fn modules-- combine to form five or six larger functional domains 1. binding sites for numerous components of ECM such as collagens, proteoglycans, and other fibronectin molecules -these binding sites facilitate interactions that link these diverse molecules into a stable, interconnected network 2. binding sites for receptors on the cell surface -these sites hold ECM in a stable attachment to the cell ** plays important role in cellular migration and reorganization during development

laminin

-family of extracellular glycoproteins that consist of three different polypeptide chains linked by disulfide bonds and organized into a molecule resembling a cross with three short arms and one long arm -can greatly influence a cel's potential for migration, growth, and differentiation -binding site for cell-surface receptors and ECM molecules ex: the primordial germ cells possess a cell-surface protein that adheres strongly to one of the subunits of the laminin molecule

integrins

-interactions of cells with extracellular materials -most important family of receptors that attach cells to their extracellular microenvironment is the ________ -on one side of the plasma membrane, _____ bind to (ligands) that are present in the extracellular matrix -on the intracellular side, they interact either directly or indirectly with dozens of different proteins to influence the course of events within a cell. -composed of two membrane spanning polypeptide chains, (a and B), that are non-covalently linked -18 different a subunits -8 different B subunits -key role in integrating the extracellular and intracellular environments. functions: -link cells to substratum -participate in cell signaling

cadherins

-mediate ca2+ dependent cell-celll adhesion and transmit signals from ECM to cytoplasm -bind to other cadherins -E- cadherin = epithelial -N= neutral -P= placental

extracellular matrix

-organized network of extracellular materials that surround the animal cells -determines the shape and activities of the cell -fibrous proteins and carbohydrates: capable of binding to receptors situated on the cell surface 1. collagen -fibrilar collagen (1, 2, 3) -non fibrillar collagen (4) 2. proteoglycans 3. fibronectin 4. laminin -integrins

selectins

-plasma membrane of leukocytes -integral membrane glycoproteins that bind to oligosaccharide sequences ** require calcium 1. E-selectin = endothelial cells 2. P-selectin = platelets and endothelial cells 3. L-selectin = leukocytes (WBCs) -binding of selectins to their carbohydrate ligands requires calcium -mediate transient cellular interactions between circulating leukocytes and vessel walls at sites of inflammation and clotting

laminin and collagen (4)

-thought to form separate, but interconnected, networks -these interwoven networks give basement membranes both strength and flexibility

hemidesmosome

-tightest attachment between a cell and its extracellular matrix is seen where cells are anchored to the underlying basement membrane -contains a plaque on the inner surface of the plasma membrane with filaments coursing outward toward the cytoplasm. -keratin= supportive function -the keratin filaments of the hemidesmosomes are linked the the ECM by integrins -integrins transmit signals from the ECM that affect the shape and activities of the attached epithelial cells.

desmosomes

...

1. selectins 2. immunoglobins 3. integrins 4. cadherins

integral membrane proteins of cell to cell interaction

focal adhesions

anchoring ECM to cells interior (outside-in signaling) when fibroblasts or epithelial cells spread onto the bottom of a culture dish, the lower surface of the cell is not pressed uniformly against the substratum. -instead, the cell is anchored to the surface of the dish only at scattered, discrete sites called _________ -dynamic structures that rapidly disassemble if the adherent cell is stimulated to move or enter mitosis -loaded with integrins

1. focal adhesions 2. hemidesmosomes

examples of cell-substrate interactions The role of integrins in making the connenciton between the ECM and the cytoskeleton is best seen in two specialized structures:

1. cell adhesion 2. proliferation 3. survival

focal adhesions may act as a type of sensory structure,collecting information about the physical and chemical properties of the extracellular environment and transmitting that information to the interior of the cell, may lead to changes in ______

arginine-glycine-aspartic acid (RGD)

many of the extracellular proteins that bind to integrins do so because they contain the amino acid sequence ________ -this tripeptide is present in the cell binding sites of proteoglycans, fibronectin, laminin, and various other extracellular proteins.

integrins

the plasma membrane in the region of focal adhesions contains large clusters of ______ -the binding of extracellular ligands, such as collagen and fibronectin, is thought to induce conformational changes in the cytoplasmic domains of the integrins that cause the integrins to become linked to actin filaments of the cytoskeleton. -linkages with the cytoskeleton lead to the clustering of integrins at the cell surface -linkages with the cytoskeleton are mediated by various actin-binding proteins, such as talin and a-talin, that bind to the B subunit of the integrin. -the cytoplasmic domains of integrins are also associated wtih protein kinases, such as FAK and Src. -the attachment of the integrin to an extracellular ligand can activate these protein kinases and start a chain reaction that transmits signals thoughout the cell. -the association of myosin molecules with the actin filaments can generate traction forces that are transmitted to sites of cell-substrate attachment

collagen and proteoglycans

together these two give cartilage and other extracellular matrices strength and resistance to deformation.