Last edited: 1/3/2022

CELL JUNCTIONS
Cell Biology | Cell Junctions Medical Editors: Aldrich, Sarah & Camille

OUTLINE (C) TYPES

I) INTRODUCTION
II) TIGHT JUNCTIONS
III) HEMIDESMOSOMES
IV) GAP JUNCTIONS
V) SUMMARY
VI) REVIEW QUESTIONS
VII) REFERENCES

I) INTRODUCTION

(A) DEFINITION

Overview of each types of cell junctions

Figure 1. Cell junction
(1) Tight junctions
Cell junctions are little adhesions that are forming
between cells (i) Proteins
(B) FUNCTIONS o Occludins
o Claudins
(1) Hold two adjacent cells together o Zona occludins
If we have two adjacent cells and certain proteins that (ii) Function
were anchored between two cells
o Hold them together o Diffusion barrier
 Block things from moving between cells
If there are any kinds of shearing forces, stretching, or
abrasive forces
→ Resist the separation of the cells (2) Adherence junction
(2) Diffusion barrier Much stronger than tight junction
o Really good for shearing forces and abrasive
forces
o And we don’t want certain things to move through (3) Desmosome
o Tight junctions can block them → act like a diffusion
Toughest and really high tensile against high shearing
barrier
forces and abrasive stretch
(3) Allow cell communication
(4) Gap junction
Little channels that exist between the two cells
Good for cell-to-cell communication
o Allows cell communication
(5) Hemidesmosome
(4) Connects cell to the basal lamina
Connects cell to the basal lamina/extracellular matrix
Structure under the cells → basal lamina / extracellular
matrix (ECM)
o Basal lamina is a little bit of connective tissue Note
Besides connecting cell-to-cell, adhesion molecules also When learning about cell junctions, we have to know the
connect cell to the basal lamina o Structure
 This makes up basement membrane o Function
o Clinical significance

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 II) TIGHT JUNCTIONS
(A) STRUCTURE (B) FUNCTION

Figure 2. Tight junctions

(1) Claudins and occludins (1) Tightly hold the cells

Claudins and occludins are two particular proteins that Explained within the name → tightly hold the cells
come out from the cell membrane into the ECM together
o And interact with one another in the space between
the cells o Basal surface of the cell
o Anchoring two cells o Apical surface of the cell
Tight junction connects cell-to-cell at the apical surface
(2) Zona occludins
Located on the cytosolic side (2) Diffusion barrier
Different types of zona occludins Imagine Na+ or K+ ion or protein molecule that we don’t
o ZO-1 want them to be able to move between the cells
o ZO-2 o They act as diffusion barrier
o ZO-3 o Block the transport of ions and different types of large
Zona occludins are bound to occludins and claudins molecules between the cells

(3) Actin filaments

Located at inner cytosolic side
Actin filaments are bound to the zona occludins

Test questions
Q1: The actual part of the protein that spans through
the cell membrane out to the extracellular component
and attaches cell to cell
→ A: Claudins and occludins
Q2: Proteins on the cytosolic side that is bound to
those actual transmembrane proteins
→ A: Zona occludins
Q3: Proteins that are bound on the most inner cytosolic
side to the zona occludins
→ A: Actin filaments

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 (C) LOCATION

(1) Blood-brain barrier (BBB) (3) Respiratory tract

(4) Kidney
We have capillary, basal lamina, and astrocyte
In between endothelial cells of the capillary there are tight
junctions
We don’t want some type of amino acid or protein get into
the areas where the neurons are at
(2) GI tract

Subtype of tight junction in kidney → leaky junctions

o Located in the proximal convoluted tubule (PCT)
o Allow certain ions to be able to pass through
 Na+, K+, Cl-
o Also allow H2O to pass
We also want to prevent certain type of pathogens and
molecules that are in our GI tract from getting in into the
actual blood
Tight junctions control the movement of certain types
of molecules from the actual lumen into the bloodstream
o Especially in the stomach
Cells tightly bound to one another in the stomach
o If we have some separation between them
 HCl can seep in between those cells
 And cause destructive lesion

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 (D) CLINICAL SIGNIFICANCE

Pathogens
o Helicobacter pylori
o Clostridium difficile
These pathogens release toxins that cause the destruction of the tight junctions
o It will form kind of a little space between the cells
→ Easily allow certain types of molecules to be able to go in and out between the cells
(1) Stomach → Helicobacter pylori (2) GI tract → Clostridium difficile

Because of the separation, it allows HCl to start eroding Water and different ions leaking out → diarrhea
its way through → forming ulcers o Disease caused by Clostridium difficile is called
o Disease caused by H. pylori is called peptic ulcer Clostridium difficile associated diarrhea
disease Separation between those cells allowing for things easily
be able to get pulled into the lumen of the GI tract
o Also more inflammatory molecules and pathogens
can actually leak into the bloodstream

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 III) HEMIDESMOSOMES
Hemidesmosomes are technically not true cell-to-cell junctions; they are cell-to-extracellular matrix junctions or cell-to-
basal lamina junctions

(A) COMPONENTS (C) PATHOLOGY

Basal Lamina (blue) Dysfunctions of the hemidesmosomes affect epithelial
o A layer of extracellular matrix secreted by epithelial tissues (e.g. skin, respiratory tract, GI tract, urogenital
cells tract), most especially the skin
o Anchors epithelial cells to the underlying connective
(1) Bullous Pemphigoid
tissue
o Made up of the following proteins: Recall:
 Fibronectin o The stratum basale anchors the epidermis to the
 Laminin dermis below
 Collagen o In between the stratum basale and the dermis is the
Integrins (purple) basal lamina
o Proteins which span through the entire cell membrane In this condition, the body has plasma cells which
and connects the cell to the basal lamina produce autoantibodies targeting integrins
Intermediate Filaments (orange) When the integrins are destroyed by the autoantibodies,
o Located along the inner cytosolic side of the cell the connection between epithelial cells and basal lamina
membrane is destroyed and they separate
o Anchor the transmembrane proteins/integrins down Results in subepidermal blisters and ulcers
o Include keratin o The blisters exhibit positive Nikolsky sign, where
slight rubbing of the skin results in exfoliation of the
outermost layer or ulceration
Involves the following:
o Axilla
o Anogenital area
o Inguinal areas
o Trunk
Spares the oral mucosa

Figure 3. Components of the Hemidesmosome

(B) FUNCTION
Hemidesmosomes form and maintain the connection
between the epithelial tissue and the basement
membrane

Figure 5. Bullous Pemphigoid

Figure 4. Epithelial Cell & Basement Membrane

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 IV) GAP JUNCTIONS
Gap junctions are the primary line for cell-to-cell communication
They are not diffusion barriers, resist abrasive forces, they don’t really connect cell to connective tissue

(A) COMPONENTS (B) FUNCTION

Connexons Facilitates cell-to-cell communication
o Form the gap junctions
(1) Intracellular Ions
o A gap junction has two connexons
Connexins Intracellular ions (e.g., sodium, calcium) can move from
o Form the connexons one cell to another through gap junctions
o A connexon has six connexins Important in cells that are “excitable” (i.e., cells which
o A gap junction has twelve connexins need to propagate electric potentials to nearby cells)
Excitable cells include:

 Has intercalated discs (composed of desmosomes

and gap junctions)
o Smooth muscle tissue
 Located along the gastrointestinal tract, respiratory
tract, urogenital tract, and blood vessels
o Neurons
 Some specific types of neurons communicate via
gap junctions

Figure 6. Components of Gap Junctions

Figure 7. Excitable Tissue
(2) Cell Signaling Molecules
Cell signaling molecules (e.g., proteins, second
messenger molecules) to move from one cell to another
Cell signaling molecules include:
o Cyclic AMP – activates protein kinase A
o IP3
When a ligand binds to the receptor on the cell
membrane, it can stimulate the cell signaling molecules
to travel through the gap junction to alert nearby cells

(i) Role in Pathology

o When a cell is infected by a pathogen, it can alert the
cell nearby to:
 synthesize antimicrobial proteins against the pathogen
 trigger apoptosis (programmed cell death)
 trigger cellular adaptive processes (e.g.,
hypertrophy, atrophy)

Figure 8. Cell Signaling in response to a Pathogen

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 V) SUMMARY
Functions Location Pathology Components Diagram

Tightly hold the cells together Blood brain barrier Destruction of the tight junction in Spans from the cell
Diffusion barrier (BBB) GI tract by toxins released by these membrane to ECM
(1) Tight Junctions

GI tract pathogens o Claudins & occludins

Respiratory tract o Helicobacter pylori Cytosolic side and
Kidney  Peptic ulcer disease bound to claudins &
Leaky junction occludins
o Clostridium diarrhea
 Clostridium difficile o Zona occludins
associated diarrhea Inner cytosolic side
o Actin filaments
Cadherin-containing anchoring junctions that GIT When cancer develops, mutated E. Cadherins
bind the membranes of adjacent cells, giving Respiratory tract genes alter the structure of the Vinculin
Junctions
(2) Adherens

strength and rigidity to the entire tissue. Urinary tract Cadherin proteins. Results in loss of Catenin
Blood vessels their function and the cells being to Actin filaments
Skin separate in clumps
These clumps spread from a primary
location to a secondary location in a
process known as: METASTASIS
Desmosomes provide high tensile strength and Cardiac Tissue Pemphigus Vulgaris: autoantibodies Cadherins
(3) Desmosomes

abrasive/ shearing force that keep cells tightly (intercalated discs) attack the desmoglein and the cells of o Desmoglein
together. the epidermis separate causing blister o Desmocolin
Skin Tissue (Epidermis) and ulcers. This usually involves the
oral mucosa. Desmoplakin
Intermediate filaments

Form and maintain the connections between the Epithelial tissues Bullous Pemphigoid Basal Lamina
epithelial tissue and the basal lamina o Skin o Autoantibodies target and destroy Integrins
o Respiratory tract integrins Intermediate Filaments
o Epithelial cells and basal lamina
(4) Hemidesmosomes

o GI tract
Urogenital tract separate, resulting in
subepidermal blisters and ulcers
o Exhibit positive Nikolsky sign
o Involves the following:
 Axilla
 Anogenital area
 Inguinal area
 Trunk
Spares the oral mucosa
Allows cell-to-cell communication (via the “excitable” tissues Connexons
passage of intracellular ions and cell signaling o Cardiac tissue o Two connexons form
(5) Gap Junctions

molecules) o Smooth muscle tissue one gap junction

In the presence of a pathogen, gap junctions Connexins
facilitate cell-to-cell communication which alerts o Neurons
Six connexins form one
nearby cells to: connexon
o synthesize antimicrobial proteins
o trigger apoptosis
trigger cellular adaptive processes

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 10) Bullous pemphigoid involves the following except:
VI) REVIEW QUESTIONS a) Oral mucosa
b) Axilla
1) Which are below are cell junctions, EXCEPT?
c) Trunk
a) Tight junction
d) Axilla
b) Areolar junction
c) Desmosome 11) Which of the following is false regarding gap
d) Hemidesmosome junctions?
a) Gap junctions are important in “excitable” tissues
2) Which cell junction below that primarily allows cell
communication? b) Gap junctions are made up of 12 connexins
a) Tight junctions c) Gap junctions play an important role in fighting off
b) Desmosome pathogens
c) Gap junction d) Gap junctions function primarily to resist abrasive
d) Hemidesmosome forces

3) Which protein of tight junction that located at the CHECK YOUR ANSWERS
cytosolic side and bound to transmembrane
proteins? VII) REFERENCES
a) Claudins ● Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for
b) Occludins the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017
● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
c) Actin filament
Pearson; 2020.
d) Zona occludins ● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
● Urry LA, Cain ML, Wasserman SA, Minorsky PV, Orr RB,
4) We can find tight junctions primarily in these parts of Campbell NA. Campbell Biology. New York, NY: Pearson; 2020
the body, EXCEPT ● Hahn S. (2014). Ellis Englesberg and the discovery of positive
a) Bone marrow control in gene regulation. Genetics, 198(2), 455–460.
b) Blood brain barrier https://doi.org/10.1534/genetics.114.167361
● Nelson, D. L., & Cox, M. M. (2017). Lehninger principles of
c) Respiratory tract biochemistry (7th ed.). W.H. Freeman.
d) Kidney ● Reed, U. C., & Zanoteli, E. (2018). Therapeutic advances in 5q-
linked spinal muscular atrophy. Arquivos de neuro-psiquiatria, 76(4),
5) How Clostridium difficile can cause diarrhea? 265–272. https://doi.org/10.1590/0004-282x20180011
a) Clostridium difficile release toxin that causes the ● Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., &
destruction of the tight junctions → water and Walter, P. (2015). Molecular biology of the cell. New York: Garland
Science.
different ions leaking out into the lumen ● Two Mechanistic Models for Nucleophilic Substitution. (2021,
b) Clostridium difficile release toxin that causes the June 23). Retrieved August 12, 2021, from
destruction of the gap junctions → water and https://chem.libretexts.org/@go/page/106337
different ions leaking out into the lumen
c) Clostridium difficile release toxin that strengthens the
tight junctions → water and different ions leaking out
into the lumen
d) Clostridium difficile release toxin that strengthens
the gap junctions → water and different ions leaking
out into the lumen
6) Which protein is found in both adherens junction
and desmosomes?
a) Actin filaments
b) Desmoplakin
c) Cadherins
d) Vinculin
7) Which cell junction is found in intercalated discs in
cardiac tissue?
a) Adherens Junction
b) Desmosomes
c) Hemidesmosomes
d) Gap Junctions
8) In Pemphigus Vulgaris, autoantibodies attack
desmosomes which causes lesions in the
_________?
a) Respiratory tract
b) Urinary tract
c) Blood vessels
d) Skin
9) Which of the following is true regarding
hemidesmosomes?
a) Integrins can be found on the inner cytosolic side of
the cell membrane
b) They are true cell-to-cell junctions
c) They connect epithelial cells to the basement
membrane
d) They allow intracellular ions to pass from one cell to
another

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