Chapter 4 : Cell-to-Cell Communication

interaction between 2 cells directly between proteins on both cells

what is juxtacrine signaling

homophilic binding (proteins are the same on both cells)

heterophilic binding (proteins are different on each cell)

what are the 2 categories of protein binding with juxtacrine signaling

protein in cell binding to protein in ECM

in addition to proteins in 2 cells binding, what other interaction can occur with juxtacrine signaling

cell 1 releases signaling protein and it diffuses over a distance, and it binds to receptor on another cell to change signaling with that cell

what is paracrine signaling

intracellular signaling within that cell

what happens once protein binds to receptor on outside of the cell

the idea that different cell types have different affinities to each other

what is differential cell affinity

spontaneous reaggregating (binding to one another) then segregation of cell types in whcih the epidermal cells were all bound to each other and on the outside and the neural cells were all bound to each other and on the inside

when the presumptive epidermal cells and neural plate cells dissociated and combined what occurred

Townes and Holfreter

who proposed the selective adhesion hypothesis

they took cells from different tissue and at different points of development and combined them → in all cases the cells would sort out to near same cells AND they separated to where you would expect to see them in the embryo at that developmental time

what did Townes and Holfreter do to prove their selective adhesion hypothesis

Differential adhesion hypothesis → theory that cells sort out themselves in the most stable pattern

what was Steinburg’s hypothesis

1) cell A always sorts more tightly in the middle than cell B

2) cell B aways sorts more tightly in the middle than cell C

based on the hypothesis, if cells A and C are combined together, A should sort more tightly in the middle than C → AND IT DID

how did Steinburg prove his differential adhesion hypothesis

surface tension → the higher the surface tension, the tighter the cells will bind

what is cell sorting mediated by

outside of the cell

where would cells with lower surface tension be seen

cell adhesion molecules

what is responsible for the surface tension of the cells

adhering cells to one another

what are cell adhesion molecules important in

calcium-dependent adhesion molecules

what does cadherins stand for

calcium

what has to bind to cadherins for them to work properly

their sequences

what may be different between different types of cadherins

they link to actin via catenins (group of proteins) and then bind to another cadherin that also linked to actin on another cell (this brings the 2 cells together)

what do cadherins bind to for cell adhesion

1) E-cadherins → all cells early on in embryonic development

2) P-cadherins → placenta

3) N-cadherins → CNS

4) R-cadherins → retina

5) Protocadherins → lack attachment to actin and tell about cell type

where are E-cadherins, P-cadherins, N-cadherins, R-cadherins, and protocadherins

1) adhere cells to one another

2) help assemble the actin cytoskeleton (stabilize it)

3) signaling molecules → activate signaling pathways than impact gene transcription

3 roles of cadherins

the neural tissue doesn’t undergo normal morphogenesis and remains much more spread out and disorganized (neural tube doesn’t form properly) → indicates the importance of type of cadherin on correct morphogenesis

what occurred when N-cadherin was knocked out (lose-it experiment) and what does this show the importance of

insoluble network of macromolecules that are secreted by cells and surround cells

what is the ECM

signaling and cell migration

what is the ECM important in

1) proteoglycans (heparan sulfate and chondroitin sulfate)

2) collagen

3) glycoproteins (fibronectin and laminin)

what are the 3 ECM molecules

they help get paracrine factors from cell that secretes them to cell that receives them

role of proteoglycans in the ECM

provides structural support (generally most abundant protein found in animals)

role of collagen in ECM

lay down path for cell migration for cells to follow

role of glycoproteins in ECM

integrins

what are the receptors for ECM molecules

laminin and collagen providing sheet for epithelial cells to sit on

what is the basal lamina composed of

• organized in sheets or tubes

• tightly linked together

• very little ECM in between them

3 characteristics of epithelial cells

• loosely organized

• migrate individually or collectively as a group

• lots of ECM

3 characteristics of mesenchymal cells

epithelial-mesenchymal transition → cells can switch back and forth between these types of cells

what does EMT stand for

signals from paracrine factors tell cell to migrate somewhere else → cell adhesions broken and basal lamina dissolved → cell released from basal lamina as mesenchymal cell

how does cell transition from epithelial cell to mesenchymal cell

the process by which 1 group of cells changed or influences another group of cells

what is induction

a cell that produces the factor or signal that influences the other cell(s)

what is an inducer

protein made by cells that diffuse a distance and impact cells a little further away

what is a paracrine factor

cell being influenced or being induced

what is a responder

protein that can respond to the signal (responder must have this protein)

what is a receptor protein

the ability to respond to a signal (some signaling pathway in place) → cell must have receptor protein AND be able to activate correct signaling pathway

what is competence

juxtacrine → local/direct signaling

paracrine → more long-range signaling (max distance is roughly 50 cell distances)

between juxtacrine and paracrine signaling, which is local and which is long-range

morphogens

what are paracrine factors considered

diffusible molecule that determines the fate of a cell by its concentration

what is a morphogen

1 sink

how many sinks does a linear morphogen gradient have

morphogen-secreting cell (source) → localized sink for morphogen degradation

what is the start and end of a linear morphogen gradient

lots of sinks

how many sinks does an exponential morphogen gradient have

morphogen-secreting cell (source) → a constant rate of morphogen degradation throughout the tissues due to lots of sinks

what is the start and end of an exponential morphogen gradient

the different concentrations of the morphogen activate different transcription factors resulting in different gene expression and therefore different cell types

how does morphogen gradient lead to different cell expression

1) fibroblast growth factor (FGF) family

2) Hedgehog family

3) Wnt family

4) TGF-beta

4 major families of paracrine factors

ligand binds to the receptor which activates tyrosine kinase which can phosphorylate and activate proteins intracellularly

function of receptor tyrosine kinase

1) change cytoskeleton

2) change gene transcription

ultimate result of receptor tyrosine kinase

1) Delta-Notch

2) Cell-Adhesion Molecules (like cadherins)

3) Eph-Ephrins

3 major types of juxtacrine signaling

1) delta protein on signaling cell and notch protein on receiving cell bind to each other

2) the binding causes protease in receiving cell to cleave portion of Notch protein

3) the portion of Notch that was cleaved acts as a transcription factor and goes into the nucleus to impact gene expression

explain the mechanism of Delta-Notch signaling