Basic Science

Departemen Histologi
 Introduction
Cell contacts essential for higher organisation of
cells & basis of tissue & organ formation

Cell contacts with another cell & extracellular

matrix rely on:
• Cell adhession molecules in surface of the plasma membrane
• Cell Junctions à several specialized areas in plasma
membrane (stronger stability of connection and
communication ability among cells)

Cell junctions found in all type of tissue à

prominent in epithelial tissue
 Introduction cont’d
Cell Junctions
components: (depend on
types of junctions)

• Membrane proteins
• Cytoskeleton fibers
• Matrix protein in
extracellular matrix (only in
cell-matrix junctions)

Membrane proteins:
proteins found on plasma
membrane (e.g.
Connexin, claudin,
cadherin, integrin etc)
Membrane proteins
 Cytoskeletons
Cytoskeleton fibers: 3 dimensional
protein structures found in cytoplasm
(3 typesà microtubule, actin
filament/microfilament, intermediate
filament)
 Extracellular Matrix
Extracellular matrix: a complex of nonliving macromolecules
manufactured by the cells & exported into extracellular space.
Macromolecules à fibronectin, laminin, etc.
 Cell Junctions Classification:
Types Based on Function:
• Occluding junctions à Tight junctions
• Communicating junctions à Gap junctions
• Anchoring junctions à Adherens junctions (desmosomes/macula
adherens & zonula adherens), focal adhesions & hemidesmosomes
Types Based on Symmetry:
• Symmetrical junctions à tight junctions, desmosomes/macula
adherens, zonula adherens & gap junctions
• Asymmetrical junctions à hemidesmosomes
Types Based on Location:
• Between Cells à gap junctions, tight junctions,
desmosomes/macula adherens & zonula adherens
• Between Cells & matrix àfocal adhesions & hemidesmosomes
Cell Junctions Map:
 1. Occluding Junctions àTight Junctions

Also called zonula occludens

Strands of protein molecules

embeded in plasma membranes

Seals cells together in an

epithelium

Major functions:
• Determine epithelial cell polarity à creating
boundary between apical domain of plasma
membrane & basolateral domain
• Barrier : preventing small molecules (lipid &
protein) leaking & preventing free passage of
substances across epithelial layer
Permeability of tight
junctions à varies
in different type of
epithelia.
i.e. Epithelium lining
of intestine 10.000 x
more permeable to
Na+ than epithelium
lining of urinary
bladder

Epithelial cells can

transiently alter
tight junctions to
increased
permeability
i.e. Increased
permeability to
amino acids from
lumen of intestine
through epithelial
after meal
 2. Anchoring Junctions
Widely distributed à abundant in tissue
subjected to severe mechanical stress
(heart, muscle, epidermis)

Composed of 2 main classes of protein:

• Intracellular anchor protein à connected to
actin filament or intermediate filaments
• Transmembrane adhesion proteins
àconnected to extracellular matrix or
extracellular domain of transmembrane
adhesion protein of another cells

2 functional forms of anchoring junctions:

• Adherens junctions and desmosomes à hold
cells together & formed by transmembrane
protein belong to cadherin family
• Focal adhesions & The hemidesmosomes à
binds cells to extracellular matrix & formed by
transmembrane protein belong to integrin
family
 2. Anchoring Junctions cont’d
A. Adherens Junctions:

• Various forms:
• Nonepithelial tissues: small
punctate or streaklike
attachment à indirectly
connect actin filament beneath
plasma membrane of two
interacting cells à held together
by desmin or vimentin (desmin
& vimentin also cytoskeleton)
• Epithelial tissue: continous
adhesions belt (zonula
adherens) just below tight
junctions à held together
adjacent epithelial cell
membranes by cadherin
• Tight junctions needed prior
formation of adherens junctions
Zonula Adherens
 2. Anchoring Junctions cont’d

The folding of an epithelial sheet to form an epithelial tube

The oriented contraction of the bundles of actin filaments running along adhesion
belts causes the epithelial cells to narrow at their apex and helps the epithelial sheet
to roll up into a tube. An example is the formation of the neural tube in early
vertebrate development. Although not shown here, rearrangements of the cells
within the epithelial sheet are also thought to have an important role in the process
2. Anchoring Junctions cont’d
B.Desmosomes/macula adherens:
• Desmos: band, Soma: Body
• Buttonlike points of intercellular contacts
between 2 adjacent cells
• Matched structured at 2 adjacent cells
• Abundant in tissues exposed to
mechanical stress i.e. Stratified squamous
epithelium of skin
• Functions:
• Holds the cells together
• Signalling functions
• As sensors that respond to cellular &
enviromental signals by changing their
organisation & modulating their
assembly state
B.Desmosomes/macu
la adherens cont’d:

• Inside the cytosolic

membrane à
Attachment plaque
made of 12 proteins
connected to
intermediate filament
à firm adhesion
among cells à
resistance to
mechanical injury
• Autoimmune disease
à disrupt
desmosomes à
blistering of skin
 Autoimmune disease à disrupt
desmosomes à blistering of skin
 2. Anchoring Junctions cont’d

C.Hemidesmosomes:
• Half desmosomes : connect basal
surface of epithelium cells to
underlying basal lamina à increasing
stability
• Act as rivets to distribute tensile or
shearing forces through an epithelium
• Morphologically resembles
desmosomes but different in
organization & biochemical
components
• Each hemidesmosome consist of:
• Inner cytoplasmic plate à connect
to intermediate fillament
• Outer membrane plaque: connect
to basal lamina by anchoring
filament & integrins
 2. Anchoring Junctions cont’d
D.Focal adhesions:
• Enable cells to get a hold on extracellular matrix
through integrin & actin filament
• Scattered & discrete sites
• A dynamic structure à can rapidly disassemble if
adherent cell stimulated to move or enter mitosis
• Capable of creating or responding to mechanical
forces
• Found in muscles, tendon
 3. Communicating JunctionsàGap Junctions
Gap Junctions/nexus:

Cells contacts that providing cell to cell

comunications by transport of ion
& small molecules up to ± 1kDa
Found almost anywhere along the
lateral membranes of most
epithelial cell & in all types of tissue
except Skeletal muscle
Formed by 6 integral membrane
proteins called connexins à
connexon (a hollow cylindrical
structure spans the plasma
membrane)
Connexons align with connexons
partner of adjacent cells membrane
 Gap Junctions Cont’d
Gap Junctions/nexus:

Different properties of gap junctions in various tissue

14 distinct connexins

Functions:

Coupling à in exitable cells i.e. Nerve cells, cardiac muscle à

allowing action potentials spread rapidly from cell to cell
Share molecules among cells à hepatocytes released glucose,
development of ovarian follicles

Permeability of gap junctions can be regulated à rapidly & reversibly

reduced within seconds depending on internal and external stimuli
Cell JunctionsàSummary
Cell JunctionsàSummary cont’d
 References
1. Molecular Biology of the Cell, 4th edition, Bruce Alberts,
Alexander Johnson, Julian Lewis, Martin Raff, Keith
Roberts, and Peter Walter, New York: Garland Science;
2002.
2. Basic Histology Text & Atlas , 10th ed. , L. Carlos
Junquira MD, Jose Carneiro MD, Robert O. Kelley PhD,
Lange Medical Books, Mc Graw-Hill
3. Histology and Cell Biology: an Introduction to Pathology,
Epithelium, 2nd edition, Abraham L. Kierszenbaum M. D.
Ph. D, Mosby Elsevier Inc. 2007, Philadelphia.
4. Functional Ultrastructure Atlas of Tissue Biology and
Pathology. Margit Pavelka, Jürgen Roth. 2005. Springer-
Verlag/Wien. NewYork.