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M2M Final Exam > Unit IV: ECM, Epithelia, & Cilia > Flashcards

Unit IV: ECM, Epithelia, & Cilia Flashcards

1
Q

4 classes of molecules in the ECM

A

Glycosaminoglycans (GAGs), usually covalently linked to proteins to form proteoglycans

Fibrous proteins; ex: Collagen and Elastin

Proteins: Multidomain adaptor proteins (i.e. Fibronectin, Laminin) + enzymes, proteases, etc.

Water & solutes

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2
Q

GAG structure

A

Glycosaminoglycans (GAGs) are unbranched polysaccharide chains composed of disaccharide repeats, usually an amino sugar and a uronic acid; these sugars can be sulfated differently, creating functional diversity

GAGs are usually linked to proteins to form proteoglycans, except for Hyaluronan

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3
Q

6 Properties of GAGs & Function

A 
Highly negatively charged
Sulfated
Hydrated
Extended conformation
Fill large volumes relative to their mass
Readily form gels through salt bridges

GAGs function to create the hydrogel backbone of the ECM and to regulate signaling molecules in different tissues

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4
Q

Structure of proteoglycans

A

PGs are comprised of GAGs covalently linked to proteins via a special serine-tetrasaccharide linkage; PGs contain at least one GAG chain but may contain many; they may be membrane-bound, anchored via a TM core protein domain or GPI linkage

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5
Q

Collagen

A

Collagen is the most abundant protein in mammals (25% of protein mass); there are 20 different types of collagen

Collagen I is the most common form, found in connective tissues
Collagen IV is found in the basal lamina

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6
Q

Fibronectin

A

A type of multi-domain adapter protein found in the ECM; fibronectin is a dimeric glycoprotein that binds to integrins via a Fibronectin Type III repeat region containing an Arg-Gly-Asp (RGD) sequence; other domains bind collagen and self-associate to form insoluble fibronectin fibrils

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7
Q

Laminin

A

A type of multi-domain adapter protein found in the basal lamina; comprised of an alpha, beta, and gamma subunit; contains binding sites for integrins and other ECM proteins, including collagen IV

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8
Q

Metalloproteases (MMP)

A

Secreted, extracellular proteases which function to turn over the ECM; MMPs are secreted in in a pro-form and cleaved into their active form; important in tissue remodeling during development and cellular migration

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9
Q

Cell Adhesion Molecules (CAMs)

A

Cadherins
Ig Super Family (IgSF)
Integrins

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10
Q

Cadherins

A

Transmembrane glycoproteins with an extracellular domain that binds to cadherin molecules expressed on other cells (homophilic binding), stabilized by Ca2+; cytosolic C-terminal tails interact with alpha and beta catenin, which bind to actin, anchoring cadherin to the cytoskeleton

B-catenin is frequently mutated in epithelial to mesenchymal transition, leading to loss of cell-cell adhesion and invasion/metastasis

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11
Q

Ig Superfamily (IgSF) CAMs

A

Single pass TM glycoproteins that engage in homophilic binding mediated by multiple Ig domains

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12
Q

Integrins

A

Transmembrane glycoprotein composed of alpha/beta heterodimers that dimerize in different combinations to bind different ECM molecules (laminin, fibronectin, collagen, etc.); integrin cytosolic domains anchor to actin microfilaments

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13
Q

CAM-associated cytoplasmic proteins

A

The cytoplasmic tails of CAMs are linked to the cytoskeleton via proteins such as alpha and Beta catenin; mutation in these CAM-associated cytoplasmic proteins can cause loss of cell-cell adhesion and contact inhibition

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14
Q

Collagen Formation & Structure

A

Pro-collagen triple helix monomers are made within the ER; they are glycosylated and hydroxylated prior to secretion; in the ECM, cleavage of the N and C termini by procollagen peptidase allows for assembly and cross-linking of long collagen fibers

Cleavage of termini produces N-telo-peptides, which can be detected in blood & urine as a marker for bone disease

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15
Q

Role of CAMs in cells signaling

A

Ligand-bound integrin recruits pro-survival kinases (i.e. src) to initiate cell survival pathways

In suspension, cells die because cell survival pathways are not activated AND apoptosis pathways are activated via Caspase 8

Constitutive activation of src in cancer allows cellular proliferation independent of adhesion signaling

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16
Q

Role of collagen in ECM

A

Fibrillar collagen (I) forms thick, long fibers that are linked to each other and to other proteins by thin, fibril-associated collagen; networking collagens (IV) form thin sheets the basal lamina

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17
Q

Elastin

A

Protein component of the ECM; elastin monomers form randomly coiled higher order structures through covalent linkages; they are able to stretch and recoil

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18
Q

Main components of the cilium

A 
Outer sheath
Transporters 
Axoneme 
Linkage Domain 
Base anchor
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19
Q

Motile Cilium Axoneme Structure

A

Formed by a circular array of 9 microtubule doublets (A-B tubules) anchored within the basal body at the (-) end with the (+) end projecting into the cilia tip; also contains a central pair of microtubules - this is a 9 + 2 structure; motile cilia also contain axonemal dynein arms which beat between the double microtubules

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20
Q

Primary Cilum Axoneme Structure

A

9 + 0 axoneme; formed by a circular array of 9 microtubule doublets (A-B microtubules) anchored within the basal body at the (-) end; generally lacks the central pair of microtubules as well as dynein arms

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21
Q

Primary Ciliogenesis

A

Centriole duplication occurs during the G1 to S-phase transition and the older centriole becomes the mother basal body in the subsequent G1 phase, during which ciliogenesis occurs; the distal end of the basal body is capped by a ciliary vesicle and microtubules assemble into the ciliary vesicle before the entire structure fuses with the plasma membrane of the cell

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22
Q

Basal Body Structure & Function

A

Basal bodies are the core anchors from which cilia are formed; basal bodies are microtubule-rich cylinders formed from nine triplet microtubules (A-B-C tubules)

23
Q

Transition Zone

A

Links the basal body to the axoneme; this is the “gatekeeper” region that limits diffusion of membrane and soluble proteins into and out of the cilum, maintaining the unique identity of the ciliary membrane

24
Q

Intraflagellar Transport (IFT)

A

Cargo needed for the assembly and maintenance of cilia is transported along the axoneme; kinesin and IFT-B complexes direct anterograde transport; retrograde transport is mediated by dynein and IFT-A.

25
Q

General function of cilia in cell signaling

A

Cilia concentrate signals with a high receptor surface : volume ratio, and also localizes the signal within a discreet domain of the cell; cilia sense physical stimuli (mechanical, temperature, gravity), light, and chemical stimuli.

26
Q

Role of cilia in left-right axis establishment

A

During embryogenesis, an invagination of ciliated cells forms near the midplate, after anterior-posterior positioning is established - this is the “ciliary node”; nodal cilia possess a 9 + 0 organization yet they beat in a rotary fashion to produce a net leftward flow of signaling molecules, which are detected by non-motile sensory cilia to signal organogenesis specific to the future left axis of the body

27
Q

2 Examples of ciliopathies

A
  1. Bardet-Biedl Syndrome (BBS) - a highly pleiotropic disorder characterized by visual loss, polydactyly, anosmia, and renal abnormalities
  2. Polycystic Kidney Disease
28
Q

Properties of Epithelial Cells

A

Cell-cell adhesion
Arranged in layers or sheets
Polarity
Turn-over and regeneration by epithelial stem cells
Avascular - nutrients and oxygen diffuse through the basal lamina

29
Q

Functions of epithelia

A

Barrier to protect internal tissues
Selective absorbption, transport, and secretion of substances
Movement of particles & mucous
Biochemical modifications of molecules (i.e. liver)
Communication between other tissues (i.e. endocrine cells)
Reception of sensory stimuli

30
Q

Endothelium

A

An epithelial tissue that faces blood or lymph

31
Q

Mesothelium

A

An epithelial tissue that lines the enclosed internal spaces of body cavities

32
Q

Epithelial to mesenchymal transition

A

During development, embryonic epithelia disassemble and move into the mesenchymal tissues where they transform into distinct, non-epithelial cell lineages (connective tissue, blood vessels, etc.)

*Also important in the formation of some cancers

33
Q

Classification of epithelia

A

Simple - comprised of a single sheet of cells; may be squamous, cuboidal, or columnar

Stratified - comprised of multiple sheets of cells; may be squamous, cuboidal, or columnar based on the shape of the outer-most layer

Pseudo-stratified - all cells attach to basal lamina but not all cells are exposed to the apical space

Transitional - stratified epithelia that is flexible such that it becomes a single sheet when stretched (i.e. bladder)

34
Q

Transcytosis

A

The process by which substances are endocytosed from one membrane region, shuttled across the cell via vesicular transport, and exocytosed from another membrane region

35
Q

Tight Junctions (Zonula Occludens)

A

Linkages between epithelial cells formed by claudin-claudin protein interactions; provide a barrier to molecular flow between cells, forcing most transport to occur transcellularly; also limit diffusion of membrane proteins between different functional domains of the epithelial plasma membrane

36
Q

Adherens Junctions (Zonula Adherens)

A

Epithelial cell-cell attachments formed by cadherin protein complexes that interact with actin filaments via their cytoplasmic tails

37
Q

Desmosomes (Macula Adherens)

A

Epithelial cell-cell attachments formed by cadherin protein complexes that interact with intermediate filaments via their cytoplasmic tails

38
Q

Gap Junctions

A

Channels that promote rapid communication between epithelial cells through diffusion of ions and small molecules

39
Q

Basal Lamina Structure

A

Thin matrix of extracellular proteins that attaches to integrin proteins in the basolateral membrane of epithelial cells; often rich in collagen IV and glycoproteins including laminins and entactins

40
Q

Focal Adhesions

A

Sites of attachment between epithelial cells basolateral membranes and the basal lamina; formed by integrins that attach to actin via their cytoplasmic tails

41
Q

Hemidesmosomes

A

Sites of attachment between the basolateral membrane of epithelial cells and the basal lamina, formed by integrins that attach to intermediate filaments via their cytoplasmic tails

42
Q

Exocrine glands

A

Arise from invaginations of epithelial sheets; cells become specialized to secrete mucous, serous, or mixed secretions from the apical surface directly onto the surface of the epithelial sheet

43
Q

Endocrine glands

A

Arise from invaginations of epithelial sheets which bud off and detach from the epithelia during morphogenesis; they secrete hormones from the basolateral membrane into the blood stream through a series of specific transport steps

44
Q

Exocrine gland structure

A

Secretory cells that make up the secretory unit are organized into lobules called alveoli or acini, or into tubes located in the base of the gland; simple epithelium lines the ducts and may modify the secretion as it moves along the epithelial surface

An exocrine gland may possess one duct (simple gland) or multiple ducts (compound gland)

45
Q

Goblet Cells

A

Single cells imbedded within the gut epithelium that secrete mucus; basically single-cell exocrine glands

46
Q

Properties of stem cells

A

Self-renewal - generation of more stem cells
Cell division
Produce differentiated progeny

47
Q

Transit Amplifying Cells

A

Daughters of stem cells which also proliferate themselves, often at faster rates, to produce differentiated cells; intermediate cells in the stem-cell lineage

48
Q

Wnts Pathway

A

Wnt signal interacts with the Frizzled receptor, which signals APC to de-inhibit B-catenin; B-catenin enters the nucleus where it promotes cell division and inhibits cell differentiation

Mutation in the APC gene causes colon cancer

49
Q

Epitope

A

A specific region of a protein 10-15 AAs long that is recognized by an antibody

50
Q

3 layers of mucosa

A
  1. Outer epithelium
  2. Lamina propria - underlying connective tissue, rich in immune cells and small blood vessels which facilitate response to ingested foreign materials
  3. Submucosa - deeper connective tissue
51
Q

Layers of skin

A
  1. Epidermis - epithelia of the skin
  2. Dermis - Underlying connective tissue
  3. Hypodermis - Deeper connective tissue
52
Q

Microvilli

A

Cell surface protrusions that contain linear actin filaments (FH2/Formin nucleated) connected to branched actin filaments (Arp2/3 nucleated) in the cell interior; microvilli function to increase surface area, improving the efficiency of membrane transport and secretion

53
Q

Basal Lamina Functions

A

Attachment of epithelia to underlying connective tissue

Selective filtration of substances diffusing to or from epithelia

Establishment and maintenance of epithelial cell polarity

Guiding the migration of cells through connective tissues

Providing a barrier to movement of invading microbes

Control of development & organizing of epithelial cells following damage

54
Q

Carcinoma nomenclature

A

Carcinomas are cancers derived from epithelial tissue

Adenocarcinomas are cancers derived from glandular epithelium

M2M Final Exam (9 decks)

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