Cell Adhesions Flashcards
1
Q
Cell Adhesions
A
- Cells don’t operate in isolation
- Cells interact with each other to coordinate activity, direct motility, form barriers, etc
- One way that cells interact with each other is through cell adhesion molecules
- Proteins expressed on the cell surface that bind the cell to other cells
2
Q
Tight Junctions: Epithelial Barriers
A
- Tightly connect cells together to form a fence and a barrier
- A type of junciton that connect 2 cells together very tightly (Cells act in unison to compartmentalize)
- Often found in epithelial layers to differentiate between apical and basolateral compartments
- Made of primarily 2 families of proteins: claudins and occludins
3
Q
Tight Junctions: a fence and a barrier
A
- Forms a barrier (gate):
- prevents (regulates) exchange between apical and basolateral extracellular compartments
- Forms a Fence:
- Prevents diffusion exchange of basolateral and apical membrane proteins
4
Q
Tight Junction Permeability Can Be Controlled
A
- Tight Junctions form a permeability barrier but they can be leaky, and their leakiness can be controlled
- Direct action on claudins/occludins (Ex: phosphorylations) can change the permeability of the junctions
- Or interactions with the actin cytoskeleton can change permeability
5
Q
Adherens: Organizing Epithelial Layers
A
- Cause cells to adhere to one another, joining the microfilament networks across cells
- A junction that causes cells to adhere to one another (cells act a one mechanical unit - microfilament network is joined across cells)
- Often found in epithelia layers to give strength and shape to the epithelium
- Made af cadherin anchored by intracellular catenins that attach to the actin cytockeleton
6
Q
Adherens Regulation
A
- Adherens junctions are generally stable in epithelial layers, but do need to be modified at times
- especially in tissue growth or wound healing
- Adherens junctions interact significantly with the actin cytoskeleton and can be regulated through that interaction
- Stimulus through Rho/ROCK can cause contraction of the actin cytoskeleton leading to tnsion through the adherens junctions and tissue modeling
- Stimulus though cdc42 can lead to removal of cadherins from the membrane and epithelial/mesenchymal transition
7
Q
Desmosomes and Intermediate Filaments
A
- A junction that causes cells to adhere to one another (cells act as one mechanical unit - intermediate filament network is joined across cells)
- Often found in basal epithelial layers to give strength to the epithelium
- Also mede of cadherin family proteins called desmocolin and desmoglein anchored through desmoplakin to the IF network
8
Q
Desmosomes Regulation
A
- Desmosomes are relatively permanent structures
- But they still need to be remodeled at times:
- Tissue growth
- Wound healing
- Etc.
- Desmosome cadherin proteins can be regulated through PKC phosphoylation causing stronger or weaker binding
9
Q
Gap Junctions
A
- Allows communication between the cytoplasm of 2 different cells
- Gap junctions allow direct communicatino between the cytoplasm of 2 cells
- Generally let everything through with an upper limit size exclusion (~<1kKa)
- But there can be some selectivity for different solutes
- Made of connexin subunits (6 on each side)
- Many different types of connexins
- Different connexins allow passage of different sizes and types of molecules
10
Q
Gap Junction Regulation
A
- Gap junction permeability can be affected by several things
- Ex: pH, [Ca2+], extrcellular signals
- Also specific connexins can be added to or removed from the membrane
11
Q
Cadherins
A
- Calcium-dependent, homophilic cell adhesion proteins involved in tissue development and sorting and junctional complexes
- “Calcium-sensitive adhesion protein”
- Many different cadherins
- Cadherins usually bind to the same cadherin (homophilic)
- Important in:
- Anchoring juntions (adherens, desmosomes)
- Initiation of anchoring junctions
- Tissue development and sorting
12
Q
Cell Adhesion Molecules (CAMs)
A
- Immunoglobulin-like, primarily homophilic cell adhesion proteins invlved in tissue sorting and immune response
- Not calcium sensitive - immunoglobulin superfamily
- Many different CAMs
- CAM may bind to same CAM or to different proteins (homophilic or heterophilic)
- Important in:
- Tissue Sorting
- Immune Response
13
Q
Selectins
A
- A subset of CAMs that heterophilically bind to carboydrates. Involved primarily in immune response
- A family of cell adhesion molecules that bind carboydrates
- Several dfferent selectins
- Bind to specific carbohydrates (or glycoprotein) on the cell surface (heterophilic)
- Important in:
- Inflammation/Immune Response
- Uterine Implantation
14
Q
Integrins
A
- Primarily bind to extracellular matrix, but a few integrins are involved in cell-to-cell binding during immune response
- Primarily extracellular matrix binding proteins
- But some integrins are involved in cell-to-cell interactions
- Many different integrins
- Integrins are made up of a heterodimer of an a-subunit and a B-subunit
- Can be in an inactive or active state
- Integrins never bind to themselves, can bind to certain CAMS (I-CAM) or extracellular proteins (heterophilic)
- Important in (as adhesion molecule):
- Immune response
15
Q
Leukocyte Adhesion
A
- Leukocytes have specific carbohydrates on their surface that bind P-selectin, but P-Selectin is sequestered inside endothelial cells under normal conditions
- During Inflammation, P-selectin is expressed on the surface of enothelial cells and weakly binds leukocytes, causing the leukocyte to ‘roll’ along the surface
- Other inflammatory signals cause activation of Leukocyte function-associated antigen (LFA) on the leukocyte
- LFA strongly binds to ICAM-1, slowing down the leukocyte and allowing diapedesis into the tissue
