Exam 4 Lesson 39 Flashcards
What are the four requirements of multicellularity?
- cells must interact and exchange signals
- cells must adhere to one another
- cells must exchange resources
- cells must give up freedom to grow, divide, and may even have to die
colonial association of cells
temporarily associated set of cells that are not well adhered
How do cells form an aggregate?
a. interact directly through cell surface proteins
b. interact indirectly by binding to a common extracellular matrix
What is between epithelial tissue and connective tissue?
basal lamina
What is connective tissue made up of?
collagen fibers
How are mechanical stresses transmitted from cell to cell?
by cytoskeletal filaments anchored to cell-matrix and cell-cell adhesion sites
In the case of tension and compression, what role does extracellular matrix play?
it bears the mechanical stresses directly
Two types of cell surface protein interactions
homophilic and heterophilic
what is the main stress bearing component in connective tissue?
extracellular matrix
what is the main stress bearing component in epithelial tissue?
cytoskeletons of cells themselves
what are cadherins?
they are “homotypic” or “hemophilic” cell-cell adhesion molecules in animals
What is extracellular region of cadherin like?
typically, five copies of the extracellular cadherin domain. The copies are separated by flexible hinge regions.
How do extracellular cadherin domains bind at hinge regions?
Ca2+ binds the regions of each hinge, and prevents it from flexing. Form a rigid, curved structure.
How do cadherins generate cell-cell adhesion?
The cadherin domain at the N-terminal tip of one cadherin molecule binds the N-terminal domain from a cadherin molecule on another cell.
What kind of side-to-side interaction exists between cadherins on same cell?
Side to side interactions between their N-terminal head regions, resulting in a linear array that is thought to interact with similar array of another cell (like velcro)
Can cadherins act as ligands? Receptors?
Cadherins are both ligands and receptors.
What is a classical cadherin?
Cadherins that are closely related in sequence throughout their extracellular and intracellular domains. There are five of the cadherin extracellular domains. Also, single transmembrane domain.
What is a nonclassical cadherin?
More distantly related in sequence. Include proteins with known adhesive function, desmocollin and desmogleins.
Flamingo cadherin
belongs to drosophila. 7 transmembrane domain. G protein. Works with development of nervous system.
How does one create many different cadherin-like proteins from a single genomic locus?
differential splicing
How are cadherins expressed in different tissues?
Different tissues express different isoforms of cadherin, which allows for homotypic assembly.
What characterizes neural crest cells? What are they progenitors of?
They are undifferentiated and migratory.
They are progenitors of the peripheral nervous system, endocrine cells, connective tissue, melanocytes that provide pigmentation in skin and hair follicles.
How does in vitro experiment show us function of cadherin in cell adhesion?
Cells expressing no cadherin do not aggregate.
Cells expressing different cadherins sort themselves.
Aggregation is quantitative, based on the level of cadherin expression. (Cells expressing more cadherin adhere more strongly and end up internally).
What is EGTA?
a calcium ion chelator
What can EGTA do to cadherin?
make hinges fall apart
What do cadherin cytosolic domains anchor?
Proteins linked to the actin cytoskeleton. The proteins are alpha and beta catenin. alpha catenin is folded.
How do cell-cell junctions respond to increased tension?
by strengthening their actin linkages
What protein senses increase in tension?
alpha catenin
What unfolds a domain in alpha catenin?
the tension created by myosin 2 pulling on actin filament. Once domain is unfolded, vinculin can bind to it. Vinculin promotes more actin filament recruiting.
What is adherents junction?
junction of two cadherins one from each cell
How is Beta-catenin a signaling protein?
Disassembly of adherents junctions sends it to the nucleus to alter gene expression.
Three steps to assembly of an adherents junction
a. membrane protrusions initiate cell-cell contact
b. actin and cadherin recruitment expands junction
c. actin remodeling and myosin recruitment expands adherens junction
What happens when cell membranes make contact?
small cadherin and catenin clusters take shape at the contact sites and associate with actin, leading to activation of the small monomeric GTPase Rac, which regulates actin.
What is the role of Rac in creation of adherens junction?
Rac promotes addl actin protrusions in the vicinity, expanding the size of the contact zone and thereby promoting further recruitment of cadherins and their associated catenin proteins.
What is the role of Rho in creation of adherents junctions?
It shifts actin remodeling toward the assembly of linear, contractile filament bundles. It also promotes the assembly of myosin II filaments that associate with bundles of actin filaments to generate contractile activity. This generates more tension which results in more recruitment.
How are adherens junctions of SI epithelial cells shaped?
Belts of actin filaments connected by cadherin interactions between cells.
How does invagination of SI epithelial cells happen?
Contraction of the actin filament belt via myosin II changes shape of cells, causing them to form a tube.
Where are intermediate filaments only found?
in vertebrates
What cadherin-like proteins interact with intermediate filaments to “rivet” cells together?
desmosomes
Molecular components of desmosomes
Extracellular nonclassical cadherins desmoglein and desmocollin. Their cytoplasmic tails bind plakoglobin (gamma-catenin) and plakophilin, which in turn bind desmoplakin. Desmoplakin binds to the sides of intermediate filaments, thereby tying desmosome to the filament.
What is pemphigus?
autoimmune disease that attacks desmoglein causing skin blistering
multilayer structure of mouse epidermis
from outside in: keratinized squames granular cell layer prickle cell layers basal cell layer basal lamina connective tissue of dermis
what are tight junctions?
specialized connections needed by some tissues
What are tight junctions made of?
from transmembrane proteins from both cells which make up sealing strands that join between cells
claudin
main transmembrane protein forming sealing strand
occludin
second major transmembrane protein forming sealing strand. not essential for assembly or structure but is important for limiting junctional permeability.
tricellulin
third important transmembrane protein form in sealing strand. required to seal cell membranes together and prevent transepithelial leakage at the points where three cells meet.
where can tight junctions be found?
vertebrates
What kind of interactions do claudins and occludins have?
homotypic interactions
How do tight junction proteins interact?
stitch plasma membrane together tightly
prevents diffusion of solutes
prevents the flow of solutes
Roles of tight junctions
a. Barrier function. ensure transport of solutes through the cells rather than around the cells by diffusion.
b. signaling pathways from tight junction proteins help to set up the polarity of the epithelial cell
c. Fence function: block diffusion of membrane proteins in the lipid bilayer, creating distinct domains (a polarized cell)
What four types of junctions do epithelial cells use?
occluding junctions
cell-cell anchoring junction
channel-forming junction
cell-matrix anchoring junction
occluding junction
tight junction seals gap between epithelial cells
cell-cell anchoring junction
adherents junction connects actin filament bundle in one cell with that in the next cell
desmosomes connect intermediate filaments in one cell to those in the next cell
channel forming junctions
gap junction allows the passage of small water-soluble molecules from cell to cell
cell-matrix anchoring junction
actin linked cell matrix adhesion anchors actin filaments in cell to extracellular matrix
hemidesmosome anchors intermediate filaments in a cell to extracellular matrix
what are selectins?
transmembrane proteins on white blood cells (lymphocytes). Have a lectin domain that binds carbohydrates on endothelial cells. The white blood cells adhere loosely and roll along the vein. Heterophilic interaction. at extracellular lectin domain, binds to carbs.
why are selections heterophilic?
they recognize surface sugar molecules on other cells. This function is dependent on calcium ion.
How do lymphocytes breach endothelial layer at sites of inflammation?
selectins expressed by endothelial cells bind carbs on the blood cells. strong interaction to cross the endothelial cell layer is provided by integrins on the WBCs and VCAMs on endothelial cells.
VCAM
vascular cell adhesion molecules
ICAM
intercellular cell adhesion molecules
what is the role of communicating junctions?
They allow for signaling, sharing nutrients, and maintaining a common membrane potential.
connexin
four-pass transmembrane protein
connexon
six connexins assemble to form connexon, or hemichannel
intercellular channel
created by alignment of connexons
two types of intercellular channels
homotypic and heterotypic
How are gap junctions related to intercellular channels?
they are clusters of channels connecting adjacent cells
What do gap junctions allow the passage of?
ions, second messengers such calcium ion, cAMP IP3
what resembles connexins in non-metazoan animals?
innexin proteins. they form channels like connexins but have little sequence similarity.
How do gap junctions work in lens cells?
lens cells never divide and receive no blood supply but are subject to oxidation from radiation and source. They exchange nutrients like amino acids and antioxidants like ascorbate and reduced glutathione through gap junction connections.
How do gap junctions work in cardiac muscle cells?
cardiac muscle cells are connected at intercalated discs where gap junctions allow action potentials to spread between cells
what is an intercalated disc?
connection between cardiac muscle cells
How do action potentials spread between cardiac muscle cells?
they use gap junctions
three cell-cell junctional complexes
macula adherens, fascia adherens, gap junctions
macula adherens
(desmosomes) provide tight linkage between cells
fascia adherens
(like adherents junctions) link the plasma membrane to the sarcomere
How do plants connect the cytosol of adjacent cells?
Plasmodesmata, which work similarly to gap junctions to aid cell-communication in plants.
structure of plasmodesmata
a. lined with PM that is common to the two connected cells
b. fine tubular structure, the desmotubule, derived from smooth ER
