Lecture 3 - Cell Junctions & Surface Specializations Flashcards
List the calcium dependent cell adhesion molecules.
Cadherins, selectins
List the calcium independent cell adhesion molecules.
integrins, immunoglobulin superfamily
How many Ca2+ molecules does a single cadherin molecule bind? What is the result of removing the Ca2+ from a cadherin?
4, removing Ca2+ will make cadherins susceptible to proteases
What molecules mediate the interaction between a cadherin dimer and the cytoskeletal element that cadherins associate with? What cytoskeletal element do cadherins associate with?
Gamma, beta, and alpha catenins, microfilaments (actin polymers)
What amino acid sequence on cadherins facilitates both dimerization and association of pairs of dimers?
histidine-valine-alanine (HAV)
What do selectins bind primarily? What do they use to bind it?
Carbohydrates, Carbohydrate recognition domain (CRD)
Where are selectins found?
Endothelial cells, blood cells
What immune response to selectins mediate and what cell do they interact with in order to mediate this response?
Selectins are integral to inflammatory response. They control the movement of leukocytes from blood into tissues.
What are the types of selectins (3) and where is each type found?
1) P-selectin - platelets, activated endothelial cells
2) E-selectin - activated endothelial cells
3) L-selectin - leukocytes (homing receptor)
How many Ca2+ molecules does an individual selectin bind?
2
How many chains make up an integrin molecule and what are the names of these two chains? Additionally, which subunit is responsible for binding relevant molecules on the internal and external sides of the PM? What are the molecules bound by this chain?
- Integrins are made up of 2 chains. There is a 17-alpha chain and a 9-beta chain
- The beta chain is responsible for binding.
- The beta chain binds talin inside the cell and an arginine-glycine-aspartic acid (RGD) sequence on fibronectin or laminin inside the cell.
What cytoskeletal element do integrins associate with and what is the sequence of proteins that facilitates association (beginning with the molecule that directly associates with the beta chain)?
Actin, the 9-beta chain binds talin, which binds vinculin, which binds alpha-actinin, which binds actin
What association exists between the 9-beta and 17-alpha chains of integrins?
Divalent cation binding sites
What potential molecules do integrins bind outside cells?
Laminin, fibronectin, tenascin, vitronectin, collagen
What characteristic do Immunoglobulin superfamily molecules share?
Extracellular Ig-like domain
What type of adhesion is typical of N-CAMs
Homophilic
What type of adhesion is typical of ICAM-1, 2, 3; VCAM-1
Heterophilic
What is the HIV-1 receptor?
CD4
What immune cells (2) do ICAMs and VCAMs play an important role in interacting/binding?
1) T-cell interactions
2) Binding of leukocytes to activated endothelial cells
From apical to basal side of a polar epithelial cell state the typical cell junction structures
\_\_\_\_\_Apical side\_\_\_\_\_\_\_\_ Occluding junctions Zonula adherens Macula adherens Hemidesmosomes \_\_\_\_\_Basal sidee\_\_\_\_\_\_\_\_ Basement membrane (basal lamina + reticular lamina)
What cytoskeletal element are occluding junctions and gab junctions associated with?
None
What cytoskeletal element are zonula adherens associated with?
Actin filaments
What cytoskeletal element are macula adherens associated with?
Intermediate filaments
What cytoskeletal element are hemidesmosomes association with?
Intermediate filaments
What protein subunits make up an occluding junction?
OCCLUDIN, CLAUDIN, jam, afadin, nectin, ZO-1,2,3
What is the primary function of an occluding junction?
Prevent free passage across an epithelial layer (regulate paracellular pathway)
What family of molecules do nectins and junctional adhesion molecules (jams) belong to?
Ig superfamily
What gene mutation causes renal magnesium wasting syndrome, and how does this syndrome present?
Claudin 16 - leads to inability to reabsorb Mg2+ in the thick ascending limb of Henle, hypomagnesemia & seizures
What is the primary molecule/interaction responsible for zonula adherens junctions?
Association of cadherin (desmocollins and desmogleins) dimers at HAV sequences
What protein subunits make up zonula adherens?
Cadherin dimer, plaque (desmoplakin & plakoglobin), catenins (trimers that mediate interaction with actin), nectin, afadin.
What cytoskeletal element stabilizes desmosomes (macula adherens)? Also, what type of molecules make up the cytoskeletal element that stabilizes desmosomes?
Intermediate filaments, keratin and vimentin
What is desmoglein 1? Where is it located?
It is a type of cadherin. It is located in all layers of epidermis.
What is desmoglein 3? Where is it located?
It is a type of cadherin. It is located in the basal and spinous layers (deeper layers of epidermis).
Is an autoantibody-mediated blistering disease in which antibodies against desmoglein 1 cause a loss of adhesion of keratinocytes in the superficial layers of the epidermis.
Pemphigus foliaceus
What is the role of hemidesmosomes?
Anchor basal portion of cell to basal lamina
What is the only asymmetrical cell junction?
Hemidesmosome
What cytoskeletal element do hemidesmosomes bind? What part of a hemidesmosome binds these filaments? What protein makes up these filaments?
Intermediate filaments, plate, keratin
What links the plaque of a hemidesmosome to the basal lamina?
Laminin 5 anchoring filaments
What specific protein do intermediate filaments bind in a hemidesmosome?
Plectins (in the plate). These plectins then bind integrins in the plaque that link plectin to laminin 5.
What is the width of a channel created by a connexon?
1.5-2.0nm
What junction links cells chemically and electrically?
Gap junctions
How many connexins make of a connexon?
6
What connexin gene mutation leads to deafness?
Connexin 26 (this gene is highly expressed in cochlea)
What connexin gene mutation leads to Charcot-Marie-Tooth neuropathies (progressive peripheral nerve degeneration)?
Connexin 32
What connexin gene mutation leads to congenital cataracts & blindness?
Connexin 50
What is the microtubule pattern observed in both cillia and flagella?
9x2 + 2
What provides force of movement in cillia and flagella?
Dyneins: (-) end direction motor proteins
What links microtubule doublets (the 9 in the 9x2 + 2 pattern) togetehr?
Nexin
What disease is characterized by a loss of dynein function leading to ciliary dyskinesia leading to poor respiratory clearance and reproductive sterility
Kartagener’s syndrome
What is the pattern of microtubules in a basal body? Where is a basal body derived from?
Pattern: 3x9 (nine peripheral triplets)
Derived from centrioles
What is the length and diameter of a standard microvilli?
Length: 1um
Diameter: 0.08um
What is the cytoskeletal element that makes up microvilli?
Actin (microfilaments)
How do cilia beat?
Beat in synchrony with rigid forwards stroke and flexible reverse stroke
What structure exists at the base of microvilli?
Terminal web - a horizontal network of actin filaments that the core actin filaments of microvilli link into
What is the substructure of stereocilia?
A core of actin microfilaments (same as microvilli)
What is the primary distinguishable structural factor for stereocilia?
They BRANCH and are longer than microvilli.
Where are stereocilia found?
Epididymus & ear hair cells
Autosomal recessive immune system disorder characterized by recurrent infections (frequently life threatening). Caused by IMPAIRED EXTRAVASATION of PMNs & MONOCYTES due to absence or mutation of Beta2-integrins.
Leucocyte adhesion deficiency type 1 (LAD-1)
Caused by defects in fucoslyated glycoconjugates needed for the function of selectin ligands during leucocyte homing
Leucocyte adhesion deficiency type 2 (LAD-2)
Condition caused by failure of the platelet Alpha(II)bBeta3-integrin to make contacts with fibrinogen & fibrin leading to platelet dysfunction and prolonged bleeding.
Autosomal recessive Glanzmann thrombasthenia
Autosomal recessive epidermal blister condition of the skin. Failure of the alpha6- or beta4-integrin subunit to be expressed in a functional heterodimer. Causes disruption of mechanical link between the basement membrane & the basal keratinoctye layer.
Epidermolysis bullosa
Autosomal recessive condition that produces weakness related in pathology to other muscular dystrophies such as Duchenne muscular dystrophy. Caused by defect in cytoskeletal linker protein dystrophin.
Congenital myopathy muscular dystrophy (CMD)
What specific mutation causes CMD?
Laminin-alpha2-chain embedded within the muscle surrounding basement membrane.
What integrin species is primarily responsible for laminin-binding on muscle cell surfaces?
alpha7beta1D (This information is found in the notes under CMD)
Loss of which cadherin type is associated with cancer cell metastasis?
E-cadherin
Where is E-cadherin found? N-cadherin?
E-cadherin: epithelia
N-cadherin: neural cells
