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BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 1
Cells in their social context
Cell Junctions
Historically studied morphologically
Model of an intestinal wall
Occluding junctions form a selective permeability barrier across epithelial sheets
Tight junctions, also known as Zonula occludens (ZO)
Occluding junctions in vertebrates provide a barrier role in most epithelia. They prevent protein and
lipid diffusion in the plasma membrane allowing for polarization i.e. Apical vs. basolateral membrane.
Tight junctions also provide a variable permeability barrier between cells. The strength of this
permeability barrier is cell type dependent. For example, bladder epithelial tight junctions are 104 X less
permeable to inorganic ions like Na+ than intestinal epithelia.
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 2
The role of tight junctions in transcellular transport
Barrier function of tight junctions
Tight junction structure and function
Sealing strands completely encircle each cell in the epithelial sheet. Permeability decreases with an
increase in the number of sealing strands
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 3
Higher resolution model of tight junctions
Claudin and occludin also bind to peripheral membrane proteins called ZO proteins that anchor the
sealing strands to the actin cytoskeleton
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 4
Septate junctions
Occur in invertebrates like Drosophila. They are functionally similar to tight junctions, but differ in
structure and appearance.
Anchoring Junctions connect the cytoskeleton of a cell to the cytoskeleton of its neighbors or to the
extracellular matrix
Anchoring junctions provide mechanical strength. This is especially important to tissues encountering
severe mechanical stress like heart, muscle, and skin. They connect the cytoskeleton to neighboring
cells or the extracellular matrix.
Anchoring Junctions are composed primary of two main classes of proteins: Intercellular anchor
proteins and transmembrane adhesion proteins.
Types of anchoring junctions
Adherens junctions
Desmosomes
Hemidesmosomes
Focal Adhesions
Anchoring junctions in epithelia
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 5
Main classes of anchoring junction protein components
Adherens junctions connect actin filaments from cell to cell
They can also form adhesion belts (zonula adherens) in epithelial layers. The transmembrane adhesion
proteins belong to the cadherin family. The intracellular anchoring proteins include: Catenins,
Vinculin and α-actinin. Cells must be attached by adherens junctions for tight junctions to form.
Adherens junctions
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 6
Uses of adherens junctions in development
Contraction of adherens junctions is mediated by myosin motor proteins with shortening of the
intervening actin filaments
Desmosomes connect intermediate filaments from cell to cell
The type of intermediate filament attached is cell type specific, but they are keratin filaments in most
epithelial cells. The transmembrane adhesion proteins belong to the cadherin family and are called
desmoglein and desmocollin. The intracellular anchoring proteins are usually plakoglobin and
desmoplakin.
Desmosome
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 7
Anchoring junctions formed by integrins bind cells to the extracellular matrix: Focal adhesions and
hemidesmosomes
Hemidesmosomes
“Half desmosomes” that connect intermediate filaments to the basal lamina. These structures are
morphologically similar to desmosomes but use transmembrane adhesion proteins belong to the integrin
family. In this case, the extracellular domain of the integrin binds to substrate on which the cell is
growing through laminin (more later). The primary intracellular anchor protein is called Plectin.
Desmosomes and hemidesmosomes
Focal Adhesions connect actin filaments to the basal lamina
The transmembrane adhesion proteins belong to the integrin family. The uniques aspect of this junction
is that focal adhesions are regulated assemblies that are altered during cellular movement.
actin=green vinculin=red
Summary of anchoring junctions
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 8
Gap junctions allow small molecules to pass directly from cell to cell
Gap Junctions
Most cells in most tissues are in communication with neighboring cells by gap junctions
They are made up of membrane-spanning channel-forming proteins called connexins. The channels or
connexons have a maximal pore size or ~ 1.5nm that allow the passage of small molecules such as
inorganic ions, sugars, amino acids, nucleotides, etc., but not proteins.
Gap junction permeability
A gap junction connexon is made up of six transmembrane connexin subunits
Anatomy of a Gap Junction
Each connexin monomer has four membrane-spanning segments. Humans have 14 different connexin
genes. Six monomers assemble into a connexon and different connexin subunit assemblies can produce
different connexons. The connexons from adjacent cells interact to form an intercellular channel
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 9
Gap junctions have diverse functions
Electrical synapse
Direct coupling allows the propagation of an action potential from one cell to another without the
need for a chemical intermediate (much faster)
Sharing of metabolites helps coordinate activities
Glycogen breakdown in response to hormonal stimulation in the liver
Hepatocytes not directly stimulated by hormone (potentially several cell layers away from a
capillary and the source of the hormone) detect a signal by sharing a second messenger through
gap junctions
Communication during development
Communication between granulosa cells and the oocyte through gap junctions is apparently important
for oocyte maturation. Mutations in connexin37 cause infertility and disruption in the development of
both the oocyte and granulosa cells.
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 10
The permeability of gap junctions can be regulated
The primary regulators of gap junction permeability are pH and cytosolic Ca2+ concentration as well as
extracellular signals including neurotransmitters like dopamine.
Why is it necessary to regulate permeability? Cells need a way to close down these connections to
prevent widespread damage when one participant is damaged.
Summary of vertebrate epithelia junctions
In plants, plasmodesmata perform many of the same functions as gap junctions
Plasmodesmata
Since plants have a rigid cell wall, a specialized structure is required to bridge it.
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 11
Cell Adhesions
Historically studied biochemically
Cell Adhesion Molecules (CAMs)
Cell surface transmembrane proteins that are responsible for cell-cell adhesion and cell-matrix adhesion.
Some are Ca2+-dependent, while others are Ca2+-independent. CAMs were initially identified using
antibodies to cell surface molecules that were capable of inhibiting cell-cell adhesion in the test tube.
Cadherins mediate Ca2+ dependent cell-cell adhesion
Present in adherens junctions and desmosomes and found in virtually all cells and tissues
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 12
Structure and function of cadherins
Types of cell-cell adhesion
Cadherins mediate cell-cell adhesion by a homophilic mechanism
Tissue culture cells (that normally do not express N or E-cadherins) can be made to express either N- or
E-cadherin. The resulting population self selects based on homophilic interaction of the individual
cadherins.
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 13
Classical cadherins are linked to the actin cytoskeleton by catenins
Selectins mediate transient cell-cell adhesions in the bloodstream
Selectins are cell surface, carbohydrate binding proteins (lectins) that function in Ca2+-dependent cellcell adhesion in the bloodstream. They are named according to the cell type in which they are
expressed. While blood cells express L-selectins, platelets express P-selectins and activated endothelial
cells express E-selectins
The structure and function of selectins
Selectins are responsible for white blood cell adherence to endothelial cells necessary for tissue
migration. The lectin-binding domain is specific for each class of selectin.
BIOS 341 Lecture 22 Cell Junctions and cell adhesions, page 14
Members of the immunoglobulin superfamily of proteins mediate Ca2+ independent cell-cell adhesion
Neural cell adhesion molecules (N-CAMs)
Intercellular cell adhesion molecules (I-CAMs)
Structure and function of N-CAMs
Multiple types of cell-surface molecules act in parallel to mediate selective cell-cell adhesion
Summary of junctional and nonjunctional adhesive mechanism
Nonjunctional contacts may initiate cell-cell adhesions that junctional contacts then orient and stabilize