Unit IV: ECM, Epithelia, & Cilia Flashcards Preview

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

Flashcards in Unit IV: ECM, Epithelia, & Cilia Deck (54)
Loading flashcards...
1

4 classes of molecules in the ECM

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

2

GAG structure

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

3

6 Properties of GAGs & Function

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

4

Structure of proteoglycans

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

5

Collagen

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

6

Fibronectin

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

7

Laminin

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

8

Metalloproteases (MMP)

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

9

Cell Adhesion Molecules (CAMs)

Cadherins
Ig Super Family (IgSF)
Integrins

10

Cadherins

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

11

Ig Superfamily (IgSF) CAMs

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

12

Integrins

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

13

CAM-associated cytoplasmic proteins

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

14

Collagen Formation & Structure

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

15

Role of CAMs in cells signaling

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

16

Role of collagen in ECM

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

17

Elastin

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

18

Main components of the cilium

Outer sheath
Transporters
Axoneme
Linkage Domain
Base anchor

19

Motile Cilium Axoneme Structure

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

20

Primary Cilum Axoneme Structure

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

21

Primary Ciliogenesis

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

22

Basal Body Structure & Function

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

Transition Zone

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

Intraflagellar Transport (IFT)

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

General function of cilia in cell signaling

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

Role of cilia in left-right axis establishment

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

2 Examples of ciliopathies

1. Bardet-Biedl Syndrome (BBS) - a highly pleiotropic disorder characterized by visual loss, polydactyly, anosmia, and renal abnormalities

2. Polycystic Kidney Disease

28

Properties of Epithelial Cells

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

Functions of epithelia

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

Endothelium

An epithelial tissue that faces blood or lymph