Lecture 20: Cell Junctions Flashcards
What are the two main tight junction proteins
- Claudin (The main functional component)
- Occludin
Each sealing strand of tight junction is composed of a long row of ___ transmembrane adhesion proteins embedded in each of the two interacting plasma membranes
4
Functions of tight junctions
- Barrier function
- the extracellular portions of tight-junction strands function as a zipock with diversified permeability
- Fence funciton
- within plasma membranes, the strand encircle the top of individual cells to delineate the border between the apical and basolateral membrane domains, thus functions as a ‘fence’ to limit the lateral diffusion of lipids and proteins between the apical and basolateral membrane domains
- Signaling function
- The cytoplasmic portions serve a magnetic bar attracting various PDZ-containing proteins
- Establish Cell polarity
- Three conserved polarity proteins complexes control polarization processes and maintain polarity
- Par (partitioning defective), Crumbs, and Scribble
- Three conserved polarity proteins complexes control polarization processes and maintain polarity
A connexon may be made up of the same (_____) or different (_____) subunits
Same (homohexameric)
Different (heterohexameric)
What are the components of the Basal lamina (basement membrane)
- Lamina usually contains
- Laminin, type IV collagen, nidogen (all are glycoproteins), along with proteoglycan perlecan
- Lamina consists of two main classes of extracellular macromolecules
- Fibrous protein
- usually glycoproteins
- Glycosaminoglycan (GAG), a polysaccharide chain (usually covalently linked to a specific core protein to form proteoglycans)
- Fibrous protein
How do cells form a massive and strong structure
- use the strength of the extracellular matrix
- use the strength of the cytoskeleton inside the cells and on cell-cell adhesions that tie the cytoskeleton of neighboring cells together
what play a central role in anchoring junctions
- Transmembrane adhesion proteins
- span the membrane, with one end linking to cytoskeleton inside the cell and the other end linking to other structures outside the cell
- What are the two families of transmembrane adhesion proteins
- 2 families are based on the external attachments
- Cadherin:
- Mediating cell-cell connection
- Integrin:
- Mediating attachment of cells to matrix
- Cadherin:
- Two other adhesion superfamilies of cell-cell adhesion molecules are selectin and immunoglobulin (Ig)-superfamily
- Classical Cadherins cell junciton associations
adherens junctions, synapses
Desmosomal cadherin cell junction associations
- Desmosomes
- Adherens junciton
- transmembrane adhesion protein
- intracellular cytoskeletal attachment
- Intracellular anchor proteins
- Transmembrane adhesion protein
- Cadherin (classical cadherin)
- Intracellular cytoskeletal attachment
- actin filaments
- Intracellular anchor proteins
- alpha-catenin
- beta-catenin
- plakoglobin (gamma-catenin)
- p120-catenin
- vinculin
- alpha-actinin
- Desmosome
- Transmembrane adhesion protein
- Intracellular cytoskeletal attachment
- Intracellular anchor proteins
- Transmembrane adhesion protein
- Cadherin (desmoglein, desmocollin)
- Intracellular cytoskeletal attachment
- Intermediate filaments
- Intracellular anchor proteins
- Plakoglobin (gamma-catenin)
- plakophilin
- desmoplakin
Classical cadherins
- Are the main mediators of Calcium dependent adherens junctions
- form adherens juncitons
- E-Cadherin
- epithelial cells and brain
- N-cadherin
- Muscle,nerve, lens cells and fibroblast
- VE-cadherin
- Endothelial cell
- P-cadherin
- Placenta and epidermis
Nonclassical cadherins
- include desmocollins and desmogleins that form desmosome junctions, and the recently discovered large subfamilyof protocadherins, which are implicated in neuronal plasticity
- The extracellular potions and intracellular portions of the cadherin superfamily
- Extracellular
- contain multiple copies of the cadherin domain motif
- Intracellular
- are varied, thus, be able to interact with differnt intracellular ligands and components that anchor the cadherin to the cytoskeleton
Is binding between cadherins usually homphilic or heterophilic
- homophilic
- cadherin molecules of a specific subtype on one cell bind to other molecules of the same kind on adjacent cells
Role of calcium in Cadherin-mediated Adhesion
- Extracellular portion of cadherin consists of several copies of a motif called cadherin domain
- Each cadherin domain forms a rigid unit, joined by the next cadherin domain by a hinge
- Ca2+ ions bind to sites near each hinge and prevent it form flexing, so that the whole string of cadherin domains behaves as rigid rod
- when Calcium is removed, the hinges can flex, and the structure becomes floppy. At the same time, the conformaiton at the N terminus changes, weakening the binding affinity and disrupting the adhesion
- Cadherins then are degraded
Characteristics of cadherin-mediated adhesion
- typically bind to partners with low affinity
- strong attachements result from the formation of many weak bonds in parallel
- functioning like Velcro to hold cells together
- clustered side-by-side on the same cell by interactions between their N-terminal head regions, and via their attachments of their intracellular tails to other anchoring proteins
what is sorting out in terms of Cadherin-mediated adhesion
- homophilic adhesions mediate highly selective recognition, enabling cells of a similar type to stick together and to stay segregated from other types of cells
Explain how changing patterns of expressionof cadherins determines the selective assortments of cells
- Appearance and disappearance of cadherins correlate with major morphogenetic events in which tissues segregate from one another
Adherens junctions
- Essenetial part of machinery for modeling the shape of multicellular structures
- Primarily present in epithelia
- Form continuous adhesion belt (or zonula adherens) close beneath the apical face of the epithelium, encircling each of the interacting cells in the sheet
- Within each cell, a contractile bundle of actin filaments lies adjacent to the adhesion belt, oriented parallel to the plasma membrane and tehtered to it by the cadherins and their associated intracellular anchor proteins
Strucutre of Desmosome
- On the cytoplasmic surface is a dense plaque composed of different anchor proteins
- a bundle of keratin intermediate filaments is attached ot the surface of each plaque
- Proteins of cadherin family bind to the plaques and interact through their extracellular domains to hodl the adjacent membranes together by a calcium-dependent mechanism
Molecular model of the Desmosome
- The desmosomal cadherins desmoglein and desmocollinundergo homophilic and heterophilic binding
- Cytoplasmic tails of desmoglein and desmocollin bind plakoglobin (gamma-catenin) and plakophilin, which in turn bind to desmoplakin
- Desmoplakin binds to the sides of intermediate filaments, thereby tying the desmosome to these filaments
- ODP: Outer dense plaque
- IDP: inner dense plaque
Desmosomes are required in tissue with _______
- high mechanical stress
- Missense mutations in Desmocollin-2 associated with arrhythmogenic right ventricular cardiomyopathy (ARVC)
- common cause of sudden cardiac death in the young
- Desmocollin not properly inserted into membrane
- Missense mutations in Desmocollin-2 associated with arrhythmogenic right ventricular cardiomyopathy (ARVC)
The particular type of intermediate filaments attached to the desmosomes depends on the cell type: ____ filaments in most epithelial cells
keratin
What are the 4 families of transmembrane adhesion proteins
- Cadherin
- Integrins
- Selectins
- Immunoglobulin-superfamily
Tight junctions
- Are the occluding juncitons found in epithelia and endothelial sheet
- form a seal between cells
- block the backflow of nutrient molecules from the basal side of the epithelium into the gut lumen
- Form a fence between membrane domains
- confine the transport proteins to their appropriate membrane domains
- This segregation permits a vectorial transfer of nutrients across the epithelium form the gut lumen to the blood
- Recruit cytoskeleton as well as signaling molecules at their cytoplasmic side
Each sealing tstrand of tight junction is composed of a long row of ____ pass transmembrane adhesion proteins embedded in each of the two interacting plasma membranes
- 4
- Two main tight junction proteins
- Claudin (the main functional component)
- Occludin
- Two main tight junction proteins
Transmembrane proteins of Tight Junctions
- Claudin is the main transmembrane protein in tight junctions
- The claudin protein family has many members, which are expressed in different combinations in different epithelia
- Occludin is the second major transmembrane protein
- Junctional adhesion molecules (JAMs)
Junctional Complex in mature Epithelium
- Includes
- Tight junction
- Adherens junction
- Desmosome
- The positioning and organization of tight junctions in relation to these other structures depends on association with intracellular scaffold protein of the Tip (tight junction protein) family, also called ZO protein
- ZO anchors tight junctions to actin cytoskeleton
Functions of tight juncitons
- barrier functions
- Fence funcitons
- delineat border between apical and basolateral membrane domains
- Signaling functions
- Establish cell polarity
What are three conserved polarity protein complexes
- par (partitioning defective)
- Crumbs
- Scribble
Gap juncitons will allow things smaller than ___ to travel through them
1000 daltons/MW
Components of Basal lamina
- Laminin
- Type IV collagen
- Nidogen (all are glycoproteins)
- Proteoglycan Perlecan
____ and ___ serve as linker to connect the laminin and type IV collagen networks once the laminin is in place
Nidogen and perlecan
Transmembrane receptor ____ and ___ organize basal lamina assembly
Integrin and dystroglycan
The intracellular linkage of integrin Beta subunit to actin is mediated by
talin
Types of glycoaminoglycans
- Chondroitin sulfate
- Dermatan sulfate
- Heparan sulfate
- keratan sulfate
