Lecture 7 - Exam Flashcards
What are the simplest organizational structure that has attributes of life?
Cells
What does being alive mean?
To be a cell or be composed of cells?
What is built up to get to organisms?
cells -> tissues -> organs -> systems -> organisms
What allows organism to carry out essential activities?
The coordinated functioning of cells that make up higher orders of organization - form follows function
What happens in pathological tissue or tumor cells?
Loss of organization of the cells
What are tissues?
Aggregates of cells organized to perform one or more specific functions
What are the 4 main tissue types?
Epithelial, connective, muscle, nerve
How is epithelium organized?
Sheets of cells that may be flat or folded into pleats, tubes, spheres - adjacent cells directly attached and have apical top and basal bottom
What is the purpose of epithelium?
Line or cover organ surfaces and regulate transport of materials and form glands
How are the subtypes of epithelium classified? and what are some examples?
Thickness and shape of cells, cuboidal and columnar
What is connective tissue made up of?
Formed by combination of cells and an extraceullar macromolecular complex of proteins
What is the purpose of connective tissue?
To form skeletal structures, provide conduit for blood vessels and nerve, make attachment and support structure, fill in spaces and provide cushioning
How are connective tissue subtypes determined?
Composition and organization of ECM and cell populations vary
What are the types of muscle tissue?
Skeletal, smooth, cardiac
What is the specialized function of all muscle tissue?
Contraction
What is nerve tissue specialize for?
Transmission of electrical signals which regulate brain function, muscle and gland activity
What are the two major cell types of nerve tissue?
Neurons - the cells that generate and receive electrical signals
Glia - mixed population of cells that provide metabolic and structural support to neruons
What two things must cells have to work as a tissue?
Cohesion - including adhesion, common function and distribution of force and
Communication - including small molecule exchange and electrical coupling and signaling pathways
What are the major kinds of adhesive interactions?
Cell-cell junctions - to provide a barrier, hold cells together, link the cytoskeleton of adjacent cells, allow intracellular movement of small molecules
Cell-matrix interactions - adhesions that attach cells to their extracellular matrix permanently or transiently
How are adhesive interactions mediated?
Cell-Adhesion Molecules - CAMs - proteins located on cell surface involved in binding - typically transmembrane receptors that bind molecules from adjacent cells or ECM
What are the 4 families of CAMs?
Immunoglobulin superfamily (IgSF CAMs), Integrins, Cadherins, and Selectins
Which CAMs perform homophilic interactions and which perform heterophilic?
Homophilic - Cadherins and IgSF
Heterophilic - Integrins and Selectins
What are the domains of CAMs?
Intracellular domain to interact with cytoskeleton
Transmembrane domain
Extracellular domain to interacts with other CAMs either homophilically or heterophilically
What is cis (lateral) binding and what is trans binding?
Cis is the adhesions of cells on the same membrane (same cells - intra) and trans is the adhesion of cells on different plasma membranes (one cell to another - inter) - cis and trans can be combined
Which CAM does cell-matrix adhesions?
Integrins (sometimes does cell-cell)
Which surfaces on cells have more transient adhesive interactions and which have more long lasting?
Transient - apical
Long lasting - lateral and basal
What is zonula occuludens?
Tight junctions - a type of lateral cell-cell adhesive interaction - it is the most apically located, it is a belt that encircles the entire cell - and is formed by numerous membrane fusions - compartmentalize integral membrane proteins into apical and basolateral domains, and prevent free flow of water soluble molecules between cells from apical to basal (paracellular)
What are the proteins that mediate tight junctions?
Occludins, claudins (most crucial in determining tightness), JAMs, and tricellulin
What is paracellular pathway versus transcellular pathway?
Paracellular is the free flow between two cells, the transcellular is flow through one cell
What is zonula adherens?
Adhering junctions - a type of lateral cell-cell adhesive interaction - encircle the cell circumference basal to the zonula occludens - give 15-20 nm between plasma membranes of cells
What is the function of zonula adherens?
Cell adhesion - link actin cytoskeletons of adjacent cells
What mediates zonula adherens?
Cadherin - to allow extracellular domains to interact or intracellular domains to link to actin cytoskeleton via catenins
What do you need for zonula adherens to form?
Cadherin and calcium - the cadherins are calcium dependent
What is epithelial-mesenchymal transition? And what is an example?
When cells lose epithelial characteristics which allow them to move around more freely - they lose E-cadherin activity and this promotes cancer and mestastisis
What is macula adherens?
Desmosomes - a type of later cell-cell adhesion interaction - located basal to the belt junctions and distributed randomly along the lateral membrane domain - discrete spot adhesions
What is the function of macula adherens?
To provide strong spot adhesions between cells - site of intermediate filament insertion on intracellular attachment plaques
What are the belt junctions and in what order do they appear?
Occludens and adherens with occludens being more apical
What are the communicating junctions?
Gap junctions - a type of later cell-cell adhesion junction
Where are gap junctions found and what comprises them?
Located randomly along lateral membranes, comprised of packed connexons which are composed of connexins (integral membrane proteins) - from 2-3 nm intercellar channel between the two connexon plaques
What are basal cell-matrix adhesions?
Hemidesmosomes and focal adhesions
What do hemidesmosomes do and what are they made up of?
Attach the basal cell membrane to the basal lamina - involved in stabile, long-term attachments, site of keratin tonofilament attachment (IF)
What mediates hemidesmosome interactions?
Integrins which link the cell cytoskeleton to the extracellular matrix molecules in the basal lamina (like laminin and type IV collagen) providing adhesion, traction and bidirection signaling - only one attachment plaque
What is the structure of integrins?
Alpha and beta subunits to form dimer - extracellular domain binds ligands, transmembrane domain, cytosolic (intracellular) domain binds the cytoskeleton - allows for outside-in signaling and inside-out signaling - bidirectional
What do focal adhesions do and what is their structure?
Attach basal cell membrane to the basal lamina, involved in dynamic, transient attachments, site of actin filament attachment, mediated by integrins that recognize R-G-D motif - used to pull forward like in lamelipodia
What is analogous to integrin in term of it’s function in skeletal muscle cells?
Dystrophin glycoprotein complex (DGC) - binds laminin in basal lamina
What are the apical cell-cell adhesive interactions?
Selectins
What are the lateral cell-cell adhesive interactions?
tight junctions (occulens), adhering junctions (adherens), desmosomes (macula adherens), and gap junctions
What are selectins? and their structures?
An apical cell-cell adhesive interaction that mediate leukocyte - vascular cell interactions, involved in dynamic attachments and have a calcium dependent lectin domain and bind to sugars in glycoproteins
What is margination?
Selectins sit on vasculature and leukocytes are in resting state with selectin ligands/carbohydrates on outside of membrane - transiently attaches to selectin which slows leukocyte rolling motion down, until integrin on leukocyte membrane attaches to ICAM on vasculature and once it is firmly attached it squeezes through cells in the vasculature (extravasation) – heterophilic interactions occurring
What does loss of cell adhesion lead to?
Cancer metastasis, skin blistering conditions, inflammation, heart arrhythmia
What factors in adhesion lead to cancer’s invasive behavior?
Integrin signaling down regulates E-cadherin to allow for augmented increased cell motility, and integrin upregulates matrix metalloproteinases (MMPs) to degrade matrix components in basal lamina
Laminin has abnormal expression that promotes migration
What can compromise junctional complexes?
Pathogens in the gut like clostridium perfringens and heliobacter pylori which binds to zonula occludins to make them nonfunctional - can lead to ulcers
Alcohol toxins can lead to intestinal hyper-permeability or leaky gut syndrome
