Biochem: Cell Junctions and Adhesions Flashcards
Cell adhesion molecules are ______ proteins. The can bind to a variety of extracellular proteins as well as to other adhesion molecules on adjacent cells. Some have interactions with the cytoskeleton.
Transmembrane
Adhesion interaction of binding to another adhesion molecule of a different type
Heterophilic
Adhesion interaction of binding to another adhesion molecule of the same type
Homophilic
This anchorage junction and defines cell polarity and controls the passage of substances between adjacent cells. It has a BELTLIKE distribution like a ribbon internally bracing the cells cells They are associated with ______ filaments
Tight Junctions Actin Filaments
This anchorage junction that has beltlike distribution and is associated with actin filaments
Zonula Adherens or Belt Desmosome
This anchorage junction has a spotlike distribution
Macula Adherens Spotlike Desmosome
Spotlike desmosomes are associated with ______ filaments
Intermediate filaments
This anchorage junction links to the basement domain of an epithelial cell to the basal lamina.
Hemidesmosome
Hemidesmosomes have _______ filaments The aforementioned filaments in hemidesmosomes are associated with a
intermediate Plaque
These COMMUNICATING junctions connect functionally two adjacent cells. They are NOT associated with cytoskeletal components
Gap junctions
Gap junctions are formed by _______, channel like structures that enable the passage of small molecules between cells
Connexons
These are the symmetrical junctions
Tight Junctions, Belt Desmosomes (zonula adherens), desmosomes (macula adherens), and gap junctions
This is the one asymmetrical junction
Hemidesmosome
The four important families of cell adhesion molecules
Cadherins Selectins Integrins Immunoglobulin-like superfamily
This family of cell adhesion molecules exhibits calcium dependent homophilic binding. There are 40 different ones, 3 of them being most common.
Cadherins
This is an epithelial cadherin found along the lateral cell surfaces and is responsible for the maintenance of most epithelial layers
E-cadherin
This cadherin is found in the CNS, the lens of the eye, and in skeletal and cardiac muscle.
N-cadherin
This cadherin is found in the placenta
P-cadherin
This cell adhesion molecules is part of the cadherin family, and anchors epithelial cells together and allows for formation of the tight and stable epithelial layer
Desmosomes (or adherens junctions)
The special cadherins in desmosomes are called ______ and ______
Desmogleins and desmocollins
The cadherins of zonula adherins (belt desmosomes) are anchored by _______ filaments
Actin filaments
The cadherins of macula adherins (spot desmosomes) are anchored by _______ ________ filaments
Keratin intermediate filaments
This is an autoimmune disease in which the body generates antibodies against desmoglein 1, causing blisting It disrupts ______ adhesion
Pemphigus Foliaceus Keratinocyte adhesion
This is an autoimmnune disease where the body generates antibodies against desmogelin 3, It affects the….
Pemphigus Vulgaris Oral Mucosa
This family of adhesion molecules require calcium for binding, but require a carbohydrate ligand
Selectins
Each selectin has a carbohydrate recognition domain (CRD) with binding affinity to a specific _________ attached to a protein (glycoprotein) or lip (glycolipid)
Oligosaccharide
This selectin is in platelets and activated endothelial cells
P-selectin
This selectin is found only in activated endothelial cells
E-selectin
This selectin is found in leukocytes
L-selectin
The binding for selectins is ______, like for leukocytes moving along the endothelium
Transient
In selectins, _______ bound at the sides of the CRD regulates the conformation of the domain and its ability to bind carbohydrates
Calcium
This family of cell adhesion molecules is a large family of molecules, consisting of α and β chains.
Integrins
There are about __ integrin heterodimers consisting of 17 forms of α and 8 forms of β subunits. (more complex than selectins, etc)
22
Integrins conduct outside in and inside out signaling. They communicate from cell to ____ and cell to _____ They have active and inactive states.
Cell to cell Cell to matrix
Which cells are integrins in? Which cells are they particularly important for? They are also found in this anchorage junction
ALL cells Platelets and Leukocytes Hemidesmosomes
The α-actinin subunit of integrins bind to _____ The β subunit of integrins binds to ____ (check this)
Actin Fibronectin and laminin
If a prootein has a ________ in it, it will likely be an integrin
RGD (arginine glycine aspartic acid)
These contain integrins, they are asymmetrical structures anchoring the basal domain of an epithelial cell to the underlying basal lamina
Hemidesmosomes
A hemidesmisone consists of an inner cytoplasmic plate associated with…. And an outer membrane plaque linking the hemidesmosome to the basal lamina by __________ and _______
Intermediate filaments (also called keratins or tonofilaments) Anchoring filaments composed of lamina 5 and integrin α6β4
This is an autoimmune disease where the body generates antibodies to BPAG 1 and 2
Bullous Pemphigoid
In Bullous Pemphigoid, the antibodies disrupt the ______ and initiate and inflammatory reaction
Hemidesmosome
In bullous pemphigoid, the disruption of hemidesmosomes separates the ___ and ____, causing blistering
Dermis and Epidermis
In bullous pemphigoid, a circulating antibody to the BP antigen triggers a local response that induces mast cells to release ______
Eosinophil cemotactic factor (which attracts eosinophils)
In bullous pemphigoid, ECFs recruit the eosinophils which releases _____, causing the breakdown of anchoring filaments linking the attachment plaque of the hemidesmosome to the basal lamina, developing a blister
Proteases
Platelets can switch on and off, this specific type is found in blood
Platelet Integrins
This type of platelet adhesion is integrin independent, occurs on damaged vessel walls
Rolling Adhesion
This type of platelet adhesion is associated with inside out signaling, aggregated/activated platelets, and fibrinogen
Stationary Adhesion
This type of platelet adhesion is associated with outside in signaling and spread platelets
Platelet Plug
The progression of platelet adhesion/signaling
Integrin dependent, outside in, inside out
These adhesions molecules are structurally similar to immunoglobulins
Immunoglobulin like superfamily
An examples of immunoglobulin like superfamily, this is expressed when inflammation is in progress to facilitate the transendothelial migration of leukocytes
Intracellular adhesion molecule 1 (ICAM-1)
ICAM 2 is another example mentioned in the slide
This is a member of the Ig superfamily and is the receptor for HIV-1 in a subclass of lymphocytes known as T cells or helper cells
CD4
The extracellular segment of a cell adhesion molecule of CAM is folded into two or six immunoglobulin like domains, because of this, CAMs belong to the ______________ of proteins
Immunoglobulin superfamily of proteins
Ig superfamily molecules can bind to identical molecules on another cell, called…
Or they can bind to other members of the family, called
- trans-*homophilic binding
- trans*-heterophoilic binding
These two immunoglobulin like superfamilies play important roles in T cell interactions and binding of leukocytes to activated or resting endothelial cells
ICAM and VCAM (vascular cell adhesion molecule)
These two molecules are within tight junctions,
The two molecules belong to this family, because four segments of each protein span the plasma membrane
Occludin and Claudin
Tetraspanins
Other protein components of tight junctions include…
afadin-nectin protein complex
Junctional adhesion molecules (JAMs), zonula occludens (ZO) proteins ZO-1, ZO-2, ZO-3 and F-actin.
Tight junctions form a circumferential gasket that contorl the ______ pathway of molecules, or the travel of substances across the epithelium between cells
Paracellular pathway of molecules
Molecules that travel across the cell follow a ______ pathway
Transcellular pathway
This part of tight junctions is anchored to ZO-1
Afadin nectin complex
Nectins form _______ which interact with eachother through the extracellular region
What type of interaction is this?
- cis*-homodimers
- trans*-homo interaction
This part of tight junctions are associated with afadin and ZO-1
How do they interact with one another?
What do they determine about the cell?
Junctional adhesion molecules
cis-homodimers
Formation of cell polarity
The molecular basic for the formation of tight junction strands seen in freeze-fracture preparations
Occludin and Claudins
Nectins and JAMs are member of the immunoglobulin superfamily. Their structure is characterized by immunoglobulin loops, each charactized by ______ bonds.
Nectins and JAMs cis-homodimers mediate this type of cell-cell adhesion
trans-homo cell-cell adhesion
In thin sections, the intercellular space is occluded by these
What is usually found below tight junctions?
Occludin, claudins, JAMs, and nectins
Zonula adherens (or belt desmosomes)
Different adhesion molecules can act in a coordinated fashion. An example is the rolling and transmigration of _____through the endothelial layer. Selectins, integrins, and ICAMs are all involved
Neutrophils
Rolling neutrophils in circulation resist shear forces to slow them down along the ____________
Vascular endothelium
Loose adhesion to the endothelium under conditions of slow flow causethe leukocytes (neutrophils) to roll
Selectins present on the endothelial cell surface bind to __________ __________ on the leukocyte surface
Carbohydrate Ligands
Note: carbohydrate containing ligans are on the cell surface, selectins on the endothelium
Integrin receptors for _______ and _______ are rapidly activated on the leukocyte surface during rolling
Chemical mediators in the sites of inflammation stimulate the activation of integrins __ and ___
endothelial ICAM-1 and ICAM-1 ligands
ß1 and ß2
During rolling, these strengthen leukocyte binding to endothelial cell surfaces
Integrins
Transendothelial migration is mediated by _____ interaction with ligands on endothelial cell surfaces.
______ dynamics participate in this process
Integrins
F-actin
Neutrophils use a similar mechanism as rolling to escape from blood vessels, primarily _____ _______, into inflammatory sites
Post capillary venules
Part of how neutrophils escape from blood vessels, primarily postcapillary venules. Leukocytes (neutrophils) establish reversible binding between ________ induced on the endothelial cell surface and ________ on the neutrophil surface. The binding is not strong and it keeps rolling
Selectins and carbohydrate ligands
2nd step of neutrophils escaping blood vessels, a strong interaction occurs between the neutrophil and the endothelial cell for adhesion. This interaction is mediated in part by _____ on the endothelium and _______
ICAM-1 and LFA-1 (lymphocyte function associated antigen 1)
3rd step of neutrophils escaping blood vessels, neutrophils migrate across the endothelium along an _______ concentration gradient produced by phagocytic neutrophils
____ contributes to diapedesis by up regulating laminin binding ά6ß1 an ________
Infiltrating neutrophils disrupt the interaction of _____ and ______
IL-8
CD99, integrin
JAMs and vascular endothelial cadherins (VE-cadherin)
Last step of neutrophils escaping blood vessels, activated macrophages secrete TNF-ά and IL-1 to stimulate the expression of _______ by endothelial cells to keep neutrophils looming
selectins
Tight Junctions, belt desmosomes, spot desmosomes, and hemidemosomes are called _____ juctions
Gap junctions are called ______, linking adjacent cells.
Anchoring Junctions
Communicating junctions
The basic unit of a gap junction is the _____, form by 6 ______ molecules surrounding a central channel
connexon, connexin
In gap junctions, the ________ is an axial channel that allows the direct passage of small signaling molecules between adjacent cells to coordinate cell responses
Intercellular channel
Clusters of intercellular channels are known as ________ because of the narrow extracellular gap that separates the apposed plasma membranes
Gap Junction
In gap junctions, six connexin monomers asseemble to form a cylinder with a central open channel, called a…
Hexameric connexon
In gap junctions, connexons in the plasma membrane of one cell align with connexons of an adjacent cell, forming a _______ intercellular channel connecting the cytoplasm of the apposed cells
Hydrophilic
A connexin molecule (gap junctions) has how many transmembrane domains?
Four
The second to last slide is really good for review!
