Biochem: Cell Junctions and Adhesions Flashcards by Karen Homsi

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

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Adhesion interaction of binding to another adhesion molecule of a different type

Heterophilic

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Adhesion interaction of binding to another adhesion molecule of the same type

Homophilic

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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

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This anchorage junction that has beltlike distribution and is associated with actin filaments

Zonula Adherens or Belt Desmosome

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This anchorage junction has a spotlike distribution

Macula Adherens Spotlike Desmosome

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Spotlike desmosomes are associated with ______ filaments

Intermediate filaments

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This anchorage junction links to the basement domain of an epithelial cell to the basal lamina.

Hemidesmosome

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Hemidesmosomes have _______ filaments The aforementioned filaments in hemidesmosomes are associated with a

intermediate Plaque

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These COMMUNICATING junctions connect functionally two adjacent cells. They are NOT associated with cytoskeletal components

Gap junctions

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Gap junctions are formed by _______, channel like structures that enable the passage of small molecules between cells

Connexons

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These are the symmetrical junctions

Tight Junctions, Belt Desmosomes (zonula adherens), desmosomes (macula adherens), and gap junctions

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This is the one asymmetrical junction

Hemidesmosome

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The four important families of cell adhesion molecules

Cadherins Selectins Integrins Immunoglobulin-like superfamily

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This family of cell adhesion molecules exhibits calcium dependent homophilic binding. There are 40 different ones, 3 of them being most common.

Cadherins

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This is an epithelial cadherin found along the lateral cell surfaces and is responsible for the maintenance of most epithelial layers

E-cadherin

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This cadherin is found in the CNS, the lens of the eye, and in skeletal and cardiac muscle.

N-cadherin

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This cadherin is found in the placenta

P-cadherin

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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)

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The special cadherins in desmosomes are called ______ and ______

Desmogleins and desmocollins

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The cadherins of zonula adherins (belt desmosomes) are anchored by _______ filaments

Actin filaments

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The cadherins of macula adherins (spot desmosomes) are anchored by _______ ________ filaments

Keratin intermediate filaments

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This is an autoimmune disease in which the body generates antibodies against desmoglein 1, causing blisting It disrupts ______ adhesion

Pemphigus Foliaceus Keratinocyte adhesion

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This is an autoimmnune disease where the body generates antibodies against desmogelin 3, It affects the….

Pemphigus Vulgaris Oral Mucosa

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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)

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!