Exam 4 Lesson 41 Flashcards
How is plant cell wall deposited?
in layers
what do successive layers of cellulose microfibrils reflect?
adjustments of microtubule orientation
layers of plant cell wall/membrane
plasma membrane, primary cell wall, middle lamella
components of primary cell wall
cross-linking glycan, cellulose microfibril, pectin
How are cellulose microfibrils aligned?
parallel to one another and perpendicular to the axis of cell elongation
how does expansion happen?
perpendicular to the orientation of the microfibrils, allowing cell to orient growth
In connective tissue in animals, when does orientation of secreted structural fibers like collage occur?
after secretion
What does orientation of cell fibers affect?
cell migration
what are fibroblasts?
the cells mainly responsible for secreting the ECM found in connective tissue
how can fibroblasts align collagen fibrils?
they can attach to and pull on a field of randomly oriented collagen fibrils to align them. Cells then move out along the collagen array. Tendons form by this mechanism in connective tissue.
Functions of the basal lamina
a. tissue stabilization
b. isolation of cells from other cells (bbb)
c. filtering of small molecules
d. signaling for cell proliferation, survival
e. determination of cell polarity
How is basal lamina structured?
it is a two-dimensional sheet of ECM made from specialized collagens and other glycoproteins and proteoglycans.
what are laminins?
they key organizing components of the basal lamina
how do cells bind to basal lamina?
via laminin receptors (integrins)
what does basal lamina mediate?
specialized interactions between cells, such as the neuromuscular junction
what controls how cells perceive and respond to signals?
the cell wall/ECM
what does the hydrated matrix control?
the “porosity” and physiochemical conditions in the ECM (controlling pore size, pH, ion concentrations, etc.)
What does controlling pore size do?
the matrix controls the ability of certain chemicals or growth factors to move through ECM.
What happens if a particular signal molecule can’t pass through ECM?
the cell will not perceive the signal
How do signal molecules approach cell surface receptors?
Some signal molecules first bind to ECM components (like GAGs) and are then moved laterally to cell surface receptors. Others are only recognized by surface receptors if they are bound to one of the ECM components. In this case, the ECM component is a co-ligand or co-receptor.
What are integrins?
Type I membrane proteins with an N-terminal ectodomain domain and a C-terminal cytosolic domain.
What do integrins bind to?
an ECM component with their ectodomain and to anchor proteins with their cytosolic domain. The anchor protein s then link the integrins to the actin filaments.
how does fibronectin glycoprotein in ECM bind to certain integrins?
via an “RGD” motif
what is “integrin switching”?
an important part of EMT process and has major effects on properties like cell adhesion to the ECM and cell motility.
what is fibronectin?
a key organizer of the ECM
soluble proteins that form insoluble fibers on the cell surface when under tension (interactions with integrant). This is how cell controls organization of ECM supporting fibers.
what allows fibronectin to organize the ECM and bind to cells?
numerous protein-protein interaction domains
integrins can be “active” or “inactive” depending on
- whether the ectodomains are bound to the ECM
2. whether the cytosolic domains are bound to the anchor proteins
How can integrins be activated to bind ECM and actin filaments?
by “outside-in” or “inside-out” signals
Outside-in activation
RGD peptide mimics the integrin binding site on fibronectin. In response to RGD, the conformation of the integrin ectodomain changes. The change is transmitted to the cytosolic domain, exposing a strong binding site for the anchor proteins and leading to an associating with actin filaments.
Inside-out activation of integrins
different signal transduction cascades can recruit talon (an anchor protein) to bind to beta integrin, leading to a conformational change in the ectodomain (activation) and binding to ECM components
what does actin cytoskeleton promote?
cell shape change, cell spreading, secretion of materials from storage granules
what can active integrins recruit?
protein kinases to assemble signaling scaffolds
Focal Adhesion Kinase (FAK)
tyrosine kinase phosphorylates itself and other target proteins at the anchor site, leading to inhibition/disassembly of focal adhesions
what can loss of FAK lead to?
too many focal adhesions, preventing cell spreading and inhibiting migration
what does elevated FAK contribute to?
overactive cell migration
what does integrin signaling depend on?
the types of integrins expressed by cell
What does integrin signaling cooperate with?
growth factor receptors
How does integrin signaling work?
through FAK kinase and Src family kinases (SFKs) to affect numerous signaling pathways
what does integrin signaling affect?
cell proliferation survival, migration
What kind of attachment do many cells require for survival? what can failure to attach lead to?
attachment to ECM/lamina
failure to attach can lead to
a. in early mouse embryo, endoderm cells send an apoptotic signal to ectoderm cells
b. ectoderm cells attached to basal lamina survive
what is “anchorage dependence”?
some cells require attachment to ECM molecules to survive/proliferate.
Do transformed cells/tumor cells have anchorage dependence?
no
How does FAK regulate cell proliferation?
it interacts with growth factor receptors to control the ERK/MAPK pathway
do animal stem cells need to be attached to lamina to survive?
yes
what do some cells do in order to migrate?
they secrete specific proteases that degrade proteins in the ECM. Examples are matrix metalloproteases or serene proteases.
How do cells secrete degrading proteases?
some cells secrete inactive proteases into the ECM and activate them with a second secreted activator in a local region.
other cells secrete inactive proteases into the ECM, then bind them to surface receptors at particular points on the cell surface.
