Cell Connections

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Cell Connections Junctions
by Dr. Vani Gupta
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Definition and Classification of cell
junction

• Cell junction is the connection between the
  neighbouring cells or the contact between the
  cell and extracellular matrix.
• It is also called membrane junction.
• Cell junction are classified into three
  types
• a-Occluding junction
• b-Communicating junction
• c-Anchoring junction.

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Cell Adhesion Molecules (CAMs)

• Important cell surface proteins molecules
  promoting cellcell and cellmatrix interactions.
• Important for many normal biological processes
  -embryonic cell migration, immune system
  functions, wound healing.
• Involved in intracellular signaling pathways
  (primarily for cell death/survival, secretion
  etc.)

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Cell Adhesion Molecules (CAMs)

• Express 3 major domains
• The extracellular domain allows one CAM to bind
  to another on an adjacent cell.
• The transmembrane domain links the CAM to the
  plasma membrane through hydrophobic forces.
• The cytoplasmic domain is directly connected to
  the cytoskeleton by linker proteins.

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Cell Adhesion Molecules (CAMs)

• Interactions between CAMs can be mediated by

Binding of an adhesion molecule on one cell to
the same adhesion molecule on a second cell
Cadherin - cadherin
An adhesion molecule on one cell type binds to a
different type of cell adhesion molecule on a
second cell Selectins mucins
The linker molecule in most cases is Laminin, a
family of large cross shaped molecules with
multiple receptor domains.
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• These cell adhesion molecules can be divided into
  4 major families
• The cadherin superfamily
• The selectins
• The immunoglobulin superfamily and
• The integrins

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The Cadherin superfamily

• Cadherins are the most prevalent CAMs in
  vertebrates.
• 125 kD transmembrane glycoproteins - mediate
  intercellular adhesion in epithelial and
  endothelial cells by Ca2 dependent homophilic
  adhesion.
• Primarily link epithelial and muscle cells to
  their neighbors
• Form desmosomes and adherens junctions
• Play critical role during development (cell
  sorting).
• Do not interact with extracellular matrix.

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The Cadherin superfamily

• Contain a short transmembrane domain and a
  relatively long extracellular domain containing
  four cadherin repeats (EC1-EC4), each of which
  contains calcium binding sequences
• Cadherins interact with specific cytoplasmic
  proteins, e.g., catenins (a, ß and ?), as a means
  of being linked to the actin cytoskeleton.
• The binding of cadherins to the catenins is
  crucial for cadherin function.

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The Selectins

• Structural features of selectins include
• NH2-terminal C-type Ca2 dependent lectin like
  binding domain, which determines the ability of
  each selectin to bind to specific carbohydrate
  lingands.
• an epidermal growth factor-like region.
• a number of repeat sequences.
• a membrane-spanning region and
• a short cytoplasmic region

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Immunoglobulin Superfamily Molecules

• Consists of more than 25 molecules.
• Important ones being
• Intracellular adhesion molecule 1(ICAM1 CD54)
• Intercellular adhesion molecule 2 (ICAM2),
• Vascular cell adhesion molecule1 (VCAM1 CD106),
• Platelet endothelial cell adhesion molecule 1
  (PECAM 1 CD31) and
• the mucosal addressin cell adhesion molecule 1
  (MAdCAM1).

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The integrins

• Fifteen different a and eight different ß
  subunits give rise to over twently different
  heterodimeric combinations at cell surfaces.
• Bind epithelial and muscle cells to laminin in
  the basal lamina
• Allow platelets to stick to exposed collagen in a
  damaged blood vessel
• Allow fibroblasts and white blood cells to adhere
  to fibronectin and collagen as they move

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Types of cell junction in animal tissue
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Occluding Junction

• A cell-cell junction that seals cells together in
  an epithelium in a way that prevents even small
  molecules from leaking from one side of the sheet
  to the other.
• Tight Junction
• Tight Junction- occluding junctions / zonulae
  occludens - zonula occludens), are the closely
  associated areas of two cells whose
•  membranes join together forming a virtually
  impermeable barrier to fluid.
• A type of junctional complex present only in
  vertebrates.
• Consist of linear array of several integral
  proteins.
• Junctional proteins occludins and claudins
  members of IG suprfamily are transmembrane
  proteins.

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Function of Tight Junction

• Strength and stability
• Selective permeable for ions.
• Fencing function
• Maintance of cell polarity
• Blood-brain barrier
• Cludin -16 in Thick Junctions of Ascending Loop
  of henle.
• Cludin- 15 Permability of cations / anions.

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Adhering Junctions

• Desmosome- Connects intermediate filament of one
  cell with other cells.
• Claudin
• Hemidesmosome
• Desmoplakin is essential for normal desmosomal
  adhesion.

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Communicating Junction

• Cell junction which permit the intercellular
  exchange of substance are called communicating
  junction, these junction permit the movement of
  ions and molecules from one cell to another cell.
  
• a- Gap junction
• b- Chemical synapse

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Gap Junction

• Gap junctions are clusters of intercellular
  channels that allow direct diffusion of ions and
  small molecules between adjacent cells.
• At gap junctions, the intercellular space narrows
  from 25 nm to 3 nm.
• gap junctions were first discovered in myocardium
  and nerve because of their properties of
  electrical transmission between adjacent cells
  (Weidmann 1952 Furshpan and Potter 1957).

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• Low resistance intercellular junction that allows
  passage of ions and smaller molecules between the
  cells.
• It present in heart, basal part of epithelial
  cell of intestinal mucosa, etc
• Junctional unit-Connexons- 6 connexins
• Connexon of one cell have allignment with
  connexon of other cells.

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Gap Junction

• Electron microscopy of gap junctions joining
  adjacent hepatocytes in the mouse. The gap
  junction (GJ) is seen as an area of close plasma
  membrane apposition

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• Function of gap junction-
• channel passage the substance have molecular
  weight less than 1000.
• Exchange of chemical messenger between cells
• Rapid propagation of action potential from one
  cell to another cell.

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Desmosomes

• Also known as macula adherens is a cell structure
  specialized for cell-to-cell adhesion.
• Are molecular complexes of cell adhesion proteins
  and linking proteins that attach the cell surface
  adhesion proteins to intracellular keratin
  cytoskeletal filaments.
• The cell adhesion proteins of the desmosome,
  desmoglein and desmocollin, are members of the
  cadherin family.
• On the cytoplasmic side of the plasma membrane,
  there are two dense structures called the Outer
  Dense Plaque (ODP) and the Inner Dense Plaque
  (IDP).
• The Outer Dense Plaque is where the cytoplasmic
  domains of the cadherins attach to desmoplakin
  via plakoglobin and plakophillin.
• The Inner Dense Plaque is where desmoplakin
  attaches to the intermediate filaments of the
  cell.

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Desmosomes
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Hemidesmosomes

• Hemidesmosomes look like half-desmosomes that
  attach cells to the underlying basal lamina.
• Rather than using desmogleins, hemidesmosomes use
  desmopenetrin cell adhesion proteins,which are
  members of Integrin family.
• The integrin molecule attach to one of many
  multi-adhesive proteins such as laminin, resident
  within the extracellular matrix, thereby forming
  one of many potential adhesions between cell and
  matrix.

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Chemical synapse

• Chemical synapse is the junction between a nerve
  fibre and a muscle fiber or between two nerve
  fibre ,through which signals transmitted by the
  release of chemical transmitter.

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Anchoring junction.

• Anchoring junction are the junction ,which
  provides strength to the cell by acting like
  mechanical attachment.
• These junction provide firm structural attachment
  between two cells or between a cell and
  extracellular matrix
• Anchoring junction are responsible for structural
  integrity of the tissue.

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various cell junctions found in a vertebrate
epithelial cell, classified according to their
primary functions
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• Q1-which of the following is a cell adhesion
  molecule
• a-integrin
• b-lysin
• c-myosin
• d-keratin

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• Q2-desmosomes differ from tight junction because
• a-allow molecules to pass in the intercellular
  space
• b-are non-communicating
• c-are present in plants
• d-lack proteins

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• Q3-the Cell Junctions allowing exchange of
  cytoplasmic molecules between two cells are
  called
• A. Gap JunctionsB. Tight JunctionsC. Anchoring
  JunctionsD. Focal Junctions

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• 4- Desmosome has the following characters except
• a- is a disk like attachment between cells
• b- is located only between epithelial cells
• c- is specialized for adhesion
• e-is called macula adherns

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• 5- Gap junctions
• a- permit the passage of large proteins from cell
  to cell
• b- form part of the classical junctional complex
• c- exist only between epithelial cells
• d- are areas of low resistance for nerve
  stimulation

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• Q-6 Which of the following apply to intercellular
  junctions?
• a) The three major adhesive junctions of animal
  cells are adherens junctions, desmosomes and
  hemidesmosomes.
• b) Desmosomes and hemidesmosomes connect
  epithelial cells to their basement membrane and
  adjacent cells respectively.
• c) Gap junctions and plasmodesmata are homologous
  structures.
• d) The junctional complexes of gastrointestinal
  enterocytes ensure that nutrients are only
  absorbed through the spaces between the cells,
  which prevents them absorbing potentially harmful
  substances.
• ANS-a

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• Q-7 tight junction
• a-are essential for metabolic coupling
• b-dont occur in vertebrates
• c-have the closest approach of two plasma
  membranes of any junction
• d-surround connexions

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• Q-8 hemi desmosome differs from spot desmosome
  because hemi desmosome
• a-connect cell to cell
• b-connect extracellular matrix to extracellular
  matrix
• c-connect cell to extracellular matrix
• d-having tonofilament ,made up of intermediate
  filament
•  

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• Desmosomes are made-up of integral protein
• a. Integrein
• b. Connexin
• C. Selectin
• d. Claudin.

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• Hemidesmosomes are connections between
• Cell to cell
• Cell to internal organ
• Cell to matrix
• Cell to cell memberane