Lecture 1-3+chap 7 Flashcards
Epidermis
Has closely packed cells of epithelial tissue
Dermis
A type of connective tissue ( looser, farther spaced)
Fibroblasts (2)
What it is+ has
- a type of cell that contributes to the formation of connective tissue
- Have receptors that mediate interactions and transmit message
Selectins will bind to
particular arrangement of sugars in the oligosaccharides that project from the surfaces of other cells
Immunogoblin
- antibodies
- glycoproteins produced by plasma cells
Cadherins (4)
depends on+ what it does+ important factor in
- Calcium dependent
- Adhesion or transmit signals
- Cadherins typically join cells of similar type to one another and do so predominantly by binding to the same cadherin present on the surface of the neighboring cell.
- Possible the most important factor in molding cells into cohesive tissues in the embryo and holding them together in the adult (Bring similar cells together)
Cadeherin loss is associated with
Maglignancy
Cadherins are distributed along
cell surfaces or part of intercellular junctions (synapses, adherens hunctions, desmosomes)
Cadherin mediates cell-cell recognition during embryogenesis:
- Cell from different “germ” layers display distinct adhesive properties. Cadherin-Cadeherin molecular interactions help establish th spatial order of different tissues in the embryo (ectoderm on outside and mesoderm in middle).
- Experiments demonstrated that seperated cells will distribute themselves so each cell adheres to only the cells of the same type.
Immunogoblin super family (IgSF) (3)
contains … that can+ calcium+many are…
- Contain IG domains that can connect to the integrin family or connect to another lgSF
- Mediate calcium independent cell adhesion (no calcium involved in interaction)
- Many IgSF proteins are ICAMS (cell surface glycoproteins that play a crucial role in mediating cell-cell interactions, particularly in the immune system)
Integrins are some of the proteins that act as receptors for
ICAMS
E-Selectins
Present on endothelial cells
P-Selectins
Present on platelets and endothelial cells
L-Selectins
Present on all types of leukocytes (white blood cells)
Selectins (3)
Dependent+ family of+ structure
- Binding of selectins to their carbohydrate ligands requires calcium
- a family of membrane glycoproteins that bind to specific oligosaccharides
- Have a small cytoplasmic segment, a single membrane-spanning domain and a large extracellular portion
Lectins
A compound that binds to specific carbohydrate groups
Movement of neutrophils from the bloodstream during inflammation (5):
- Inflammation activates endothelial cells, which upregulates the selectins and they become more adhesive to neutrophils
- Selectins bind to the carbohydrates residue on a neutrophil , a phagocytic leukocyte
- Platelet activating factor or IL-8 on the surface of endothelial cells activates G-protein coupled receptors on the neutrophil and this leads to activation of integrin proteins (neutrophil)
- Integrin bind to ICAMs on endothelial surface and a cascade of events results in cytoskeletal rearrangement such that the cell can extravasate
- Transendothelial migration
One of the most important proteins that reduces metasis is
the presence of E-cadherin
Selectins vs Cadherins roles
- Selectins are involved in neutrophil trapping
- Cadherins are involved in cell sorting during embryogenesis
Polarized cell has a different
apical membrane than its basal membrane
Visualizing the structure of cell junctions using electron microscopy:
- uses electrons rather than light
- very high resolution (visualization) of cellular structures
- samples are imaged under a vacuum so live cells cant be imaged
Tight junctions, adherens, desmosomes
- Tight junctiuon: tighest contact sport
- adherens junction: not as close, not too much protein (dark)
- Desmosomes: Very dark (tight junction), protein heavy, contribute to tissue strength, glue cells together and keep them all in place in the tissue
Tight junctions
Where do they occur+ prevent
- They occur between neighboring epithelial cells
- They prevent solute distribution where different solute concentrations are in adjacent compartments
Tight junctions: Gate function
What it does+ claudin 1
- Control passage of molecules between cell plasma membranes
- Claudin 1 cause death due to dehydration as space in cell by gate function is failing and water escepes instead of being in the cell
Tight junctions: Fence function (3)
controls+ connects+ prevents
- Controls diffusion of integral membrane protein between apical and basal lateral membranes of a cell
- Connects to actin cytoskeleton and microtubules
- Prevents intermixing of molecules in the apical membrane with those in the lateral membrane
Tight junctions form close contacts between cells how does this happen?
- tight junction proteins such as claudins come from each cell and interact to form the junction
Tight junction proteins can interact with
actin and microtubules
Epithelial polarity
Whether the apical membrane is different from the basolateral membranes and that is controlled by tight junctions
Paracellular pathway
Passage of solids inbetween the 2 plasma membrane
Tight junctions restrict plasma membrane proteins to
a particular domain of the membrane
Adherens junction (4)
What it does+extracellular side structure+provides+present
- Connects external environment to the actin cyctoskeleton on the inside of the cell
- cells are held together by calcium-dependent linkages formed between the extracellular domains of cadherin molecules that bridge the 30–nm gap between neighboring cells
- Provides a pathway for signals to be transmitted from the exterior to the cytoplasm and nucleus
- E-cadherin present
Desmosomes (4)
inner plasma membrane+outer extrac+contains+anchors+dependent
- cadherins interact with multiple proteins to form a cytoplasmic plaque on the inner surface of the plasma membranes
- desmosomes contain cadherins that link the two cells across a narrow extracellular gap.
- on the lateral side of the endothelial cell, and they were making connections with the keratin and the intermediate filament type skeleton.
- The intermediate filament cytoskeleton anchors 2 cells together. This provides strength to a sheet of cells. (anchor inter medi. filament network to plasma membrane)
- Desomosomal cadeherins have calcium dependent binding
Keratin Intermediate filaments are in epithelial cells
- Form heterodimers (two different keratins) and form long cables
- Contribute to strength of the cell and tissue
- Mutations in keratin genes can result in skin fragility
- Gene expression and heterodimers change with cell specialization (differentiation)
The dermis consists largely of
extracellular elements that interact with each other and with the surfaces of scattered cells (primarily fibroblasts)
glycocalyx
- carbohydrate projections on the outer surface of the plasma membrane from integral membrane proteins, as well as certain membrane lipids
The glycocalyx is thought to …… (4)
- 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
basement membrane (or basal lamina)
- The basement membrane is a thin, dense layer of extracellular matrix that consists of collagen IV, laminin-entactin/nidogen complexes, and proteoglycans
- The basement membrane predominantly provides structural support as it helps cells to attach and anchor to the underlying tissues. It also acts as a barrier, preventing cancer cells from invading the deeper tissue layers, and is essential in regulating cell behavior, such as proliferation, differentiation, adhesion, or migration.
Those cells that do not lie on a basement membrane sheet, such as —–, are typically surrounded by ——.
- the fibroblasts of a connective tissue
- a less organized ECM consisting largely of thread-like fibrils
The major components of extracellular matrices include collagens, proteoglycans, and a
variety of proteins such as fibronectin, and laminin. Each of the proteins of the extracellular
matrix contains ——.
- binding sites for one another and for receptors on the cell surface
Collagens + ex (5)
present in+produce dby+ structure x2+ex
- comprise a family of fibrous glycoproteins that are present only in extracellular matrices
- Collagen is produced primarily by fibroblasts and also by smooth muscle cells and epithelial cells
- All collagen molecules are trimers consisting of three polypeptide chains, called α chains.
- Along at least part of their length, the three polypeptide chains of a collagen molecule are wound around one another to form a rod-like triple helix
- collagen 1
fibrils (2)
what they are + strengthened by
- strengthened by covalent cross-links between lysine and hydroxylysine residues on adjacent collagen molecules
- A number of the collagens, including types I, II, and III, are described as fibrillar collagens because they assemble into rigid, cable-like fibrils, which in turn become packaged into thicker fibers
The properties of a particular tissue can often be correlated with the three-dimensional organization of its collagen molecules for ex: (2)
- Tendons (muscle-bone) contain an ECM in which the collagen fibrils are aligned parallel to the long axis of the tendon and thus parallel to the direction of the pulling forces.
- The thick, middle layer of the cornea is the stroma, which contains relatively short collagen fibrils that are organized into distinct layers. The layered structure of the stroma is similar to that of plywood: the fibrils of each layer are parallel to other fibrils in the layer but nearly perpendicular to the fibrils in the layer on either side. This plywood-like structure provides strength to this delicate tissue, while the uniformity of size and ordered packing of the fibrils minimize the scattering of incoming light rays, thereby promoting the tissue’s transparency.
Not all collagens form fibrils. The distribution of one type of nonfibrillar collagen, —–, is
restricted to —–.
- type IV
- basement membranes
Type IV collagen trimer
contains nonhelical segments interspersed along the molecule and globular domains at each end.
proteoglycan (6)
consist of + chain composed of+chain is highly…+charge+binds to+assembled
- A proteoglycan consists of a core protein molecule to which chains of glycosaminoglycans (GAGs) are covalently attached
- Each glycosaminoglycan chain is composed of a repeating disaccharide; that is, it has the structure -A-B-A-B-, where A and B represent two different sugars.
- GAGs are highly acidic due to the presence of both sulfate and carboxyl groups attached to the sugar rings
- All GAGs bear large numbers of negative charges
- Bind to cell surface receptors
- Proteoglycans of the extracellular matrix may be assembled into gigantic complexes by linkage of their core proteins to a molecule of hyaluronic acid
The extracellular matrix of bone is also composed of collagen and proteoglycans because…..
Because of the negative charges borne on the sulfated GAGs, proteoglycans bind huge numbers of cations, which in turn bind large numbers of water molecules. As a result, proteoglycans form a porous, hydrated gel that fills the extracellular space like packing material and resists crushing (compression) forces. This property complements that of the adjacent collagen molecules, which resist pulling forces and provide a scaffold for the proteoglycans. Together, collagens and proteoglycans give cartilage and other extracellular matrices strength and resistance to deformation.
Fibronectin
structure+ binding site for x 2+talk abt the sepcific of each peptide +r
structure+ binding site for x 2+talk abt the sepcific of each peptide +rgd
- two polypeptide chains joined by a pair of disulfide bonds make up a fibronectin molecule
- Binding sites for numerous components of the ECM, such as collagens, proteoglycans, and other fibronectin molecules.
- Binding sites for receptors on the cell surface. These binding sites form a stable attachment between the ECM and the cell
- Each polypeptide is composed of a linear series of distinct modules, which are organized into several larger functional units, illustrated by the colored cylinders in this figure. Each of these functional units contains one or more binding sites for either a specific component of the ECM or for the surface of cells
- RGD sequence forms a loop of the polypeptide, protruding from one module
the RGD sequence
this sequence binds specifically to a particular class of integral plasma membrane proteins (integrins) that are involved in cell attachment and signal transduction
Laminins (4)
structure+influences+binds tightly to+with collagen?
- a 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
- greatly influence a cell’s potential for migration, growth, and differentiation
- binding tightly to cell-surface receptors, and can bind to other laminin molecules, to proteoglycans, and to other components of basement membranes
- The laminin and type IV collagen molecules of basement membranes are thought to form separate, but interconnected, networks. These interwoven networks give basement membranes both strength and flexibility.
ECM importance
- sends critical signals for survivial, orientation and differentiation
How do 1/2 integrins contact other proteins?
- Integrins have an RGD binding site (arg-Gly-Asp) that binds an RGD peptide in its ligand
Integrins (4)
outer+inner+composed of+orientation
- On the outer side of the plasma membrane, integrins bind to a remarkably diverse array of molecules (ligands) that are present in the extracellular environment.
- On the intracellular side of the membrane, integrins interact either directly or indirectly with dozens of different proteins to influence the course of events within the cell.
- Integrins are composed of two membrane spanning polypeptide chains, an α chain and a β chain, that are noncovalently linked.
- the two subunits are oriented to form a globular extracellular head connected to the membrane by a pair of elongated “legs”. The legs of each subunit extend through the lipid bilayer as a single transmembrane helix and end in a small cytoplasmic domain of about 20 to 70 amino acids
Integrin activation (2)
steps+ they tend to…..bc…
- Separation of the cytoplasmic tails and transmembrane domains of an integrin, which results when talin is bound, is thought to send a change in conformation through the legs of the integrin; this causes the molecule to assume an upright position in which the head of the protein is capable of interacting specifically with its appropriate ligand.
- Clustering of the activated integrins due to interactions of their cytoplasmic domains with the cytoskeleton
Inside-out signaling of integrins
- The specific binding to the cytoplasmic tail of integrin’s β subunit by the intracellular protein talin induce conformational changes in the integrin leading to increased ligand binding affinity
Outside in signaling of integrins
- signaling, binding of substrate by integrin send a siignal to focal adhesion kinase which starts a signaling cascade to the nucleus where a specific group of genes may be activated
Many of the extracellular proteins that bind to integrins do so because they contain the amino acid sequence arginine-glycine-aspartic acid (or, in abbreviated amino acid nomenclature, RGD). This is present in …..
This tripeptide is present in the cell-binding sites of proteoglycans, fibronectin, laminin, and various other extracellular proteins
Focal adhesion
- formed by the clustering of transmembrane receptors called integrins tethered at one end to the extracellular matrix (ECM) and the other to actin stress fibers, which are responsible for cell traction and ECM reorganization.
hemidesmosome (3)
structure+ unlinke FA….+linked to extracellular
- contain a dense plaque on the inner surface of the plasma membrane with filaments coursing outward into the cytoplasm
- Unlike the filaments of focal adhesions, which consist of actin, the filaments of the hemidesmosome are thicker and consist of the protein keratin. Keratin-containing filaments are classified as intermediate filaments, which serve primarily in a supportive function
- The keratin filaments of the hemidesmosome are linked to the extracellular matrix by
membrane-spanning integrins instead of cedherins in desmosomes
Four distinct families of integral membrane proteins play a major role in mediating cell–cell adhesion:
(1) selectins, (2) certain members of the immunoglobulin superfamily (IgSF), (3) certain members of the integrin family, and (4) cadherins.
Dense cytoplasmic plaques on the inner surfaces of the plasma membranes for desmosomes and hemidesmesones serve as
sites of anchorage for looping intermediate filaments
Gap junctions (4)
site of +what it is+arrangement+ allow what to pass?
- sites between animal cells that are specialized for intercellular communication
- sites where the plasma membranes of adjacent cells come very close to one another (within about 3 nm) but do not make direct contact. Instead, the cleft between the cells is spanned by very fine strands that are actually molecular “pipelines” passing through the adjoining plasma membranes and opening into the cytoplasm of the adjoining cells
- the arrangement of six connexin subunits to form a connexon, 2 connexon is a gap junction
- allow the diffusion of molecules having a molecular mass below approximately 1000 daltons
