Cell Biology Chapter 17

Cells use the cytoskeleton to:

- Generate and
maintain cell shape

- Organize compartments

- Transport materials (Diffusion is too slow and inefficient)

- Protect against mechanical stress

- Move through their environment

- Respond to intracellular & extracellular signals

Intermediate filaments are _______ nm

10

Intermediate filaments are like a _______ with high tensile strength

rope

Intermediate filament's areas of highest concentration are the ________, ________, ____________, and nerve axons

nuclear lamina, epithelia, muscle

Does Intermediate filaments have polarity?

No

Intermedia filaments are the most ______________ and they are controlled by phosphorylation

stable filaments

Intermediate filaments major functions include ___________ and protection from mechanical stress

cell integrity

Microtubules are ______ nm

25

Microtubules are __________ and are like railroad tracks

strut (resist compression)

Microtubules areas of highest concentration are the mitotic spindle, cilia, ____________, and nerve axons

flagella

Does Microtubules have polarity?

yes

Microtubules stability & assembly are ____________ controlled by GTP hydrolysis

dynamic instability

Microtubules major functions are _________, transport, mitosis, cilia, and flagella

cell polarity

Intermediate filaments (IFs) are the most __________ filaments

stable

IFs organize and ___________

interconnect tissues

IFs protect against____________

mechanical stress

IFs serve as ____________ for signaling molecules

scaffolds

IF subunits have a _________ family (>70 IF genes in humans)

Large gene

IF subunits are composed of a conserved _________ that is involved in assembly

central rod domain

IF subunits are _____________ at amino and carboxy termini, which confer specific functions

variable, unstructured domains

IFs form anti-parallel, staggered ____________. Tetramers assemble into 10 nm filaments

tetramers

8 tetramers assemble into ________ 10 nm filament

non-polarized

IFs are relatively __________ & are the most resistant to extraction of the cytoskeletal filaments. Outer layer of dead skin cells is comprised mostly of keratin

stable

Outer layer of dead skin cells is comprised mostly of _________

keratin

Four major classes of IFs are

1. Expressed in cell- and tissue-specific fashion

2. Provide each cell type with unique architecture

3. Origin of tumor cells can be identified by IF type

Four major classes of IFs are keratin filaments, vimentin and vimentin-related filaments, neurofilaments, and __________

nuclear lamins

Keratin filaments originate from the __________ and are in epithelial cells

cytoplasm

vimentin and vimentin-related filaments originate from the cytoplasm and are in connective tissue cells, __________ and glial cells.

muscle cells,

Neurofilaments originate from the cytoplasm and are in _________

nerve cells

Nuclear lamins are nuclear and are in all __________

animal cells

__________ & junctions protect epithelial cells from mechanical damage

Keratins

____________ & related proteins are found in other tissues

Vimentins

___________ support axons in nerve cells

Neurofilaments

_________ form the nuclear lamina that supports nuclear envelope

Lamins

Intermediate filaments protect cells against ___________. True in many cell types, most obvious in skin

mechanical stress

Keratins form ________ that bind to desmosomes and connect neighboring cells

basket-like arrays

Defects in keratins or junction proteins lead to _____________

cell rupture

_____________ are intercellular junctions that link the keratin filaments of one cell to those in a neighboring cel

Desmosomes

Epidermolysis bullosa simplex (EBS) is a type of ____________ where blisters form between epidermis & connective tissue

skin blistering disease

Epidermolysis bullosa simplex (EBS) is caused by a defect in keratin expressed in the ____________

bottom layer of skin

Until recently, no treatment existed beyond ____________ for Epidermolysis bullosa simplex (EBS)

wound care

Nuclear lamins form an IF network inside the nucleus

1. Two-dimensional meshwork on the nuclear envelope

2. Protects nucleus, plays a role in chromatin organization

3. Phosphorylation of lamins by kinases disassembles the network, driving nuclear envelope breakdown during mitosis

4. Dephosphorylation leads to reassembly of the nuclear lamina

Would the addition of protein kinase inhibitors enhance or disfavor the assembly of the nuclear lamina?

Enhance: Phosphorylation of lamins drives disassembly of the nuclear lamina, so inhibiting the kinases that phosphorylate lamins will enhance assembly

Would the addition of protein kinase inhibitors enhance or disfavor the addition of phosphatase inhibitors>

Disfavor: Dephosphorylation of lamins promotes reassembly of the nuclear lamina, so inhibiting the phosphatases that dephosphorylate lamins will disfavor assembly

__________ are hollow tubes with structurally distinct ends

Microtubules (MTs)

Microtubules (MTs) organize the ________ of the cell

interior

The _________ is the major Microtubule (MT)-organizing center

centrosome

Microtubule (MT) networks are maintained by ___________

assembly & disassembly

Growing microtubules exhibit ___________

dynamic instability

In Mircrotubules, ___________ drive intracellular transport

motor proteins

There are that organelles move along ____________

microtubule track

Cilia & flagella contain microtubules moved by ____________

dynein

MTs are hollow tubes with structurally distinct ends

1. Largest, most rigid filament

2. Major architectural strut that resists compression

3. Primary intracellular railroad track

4. Primary determinant of cell polarity

The building block of MTs is the __________

a/b tubulin heterodimer

Microtubules (MTs) are hollow tubes made of 13 ___________. Each protofilament is a linear chain of tubulin dimers

protofilaments

MTs have _________ & minus (slow-growing) ends

plus (fast-growing)

____________ are usually located near the nucleus in the cell center

Centrosomes

In most animal cells, the centrosome organizes an array of ___________ that radiates outward through the cytosol

MTs

Centrosomes are duplicated to form the ___________

mitotic spindle poles

Microtubule-organizing centers (MTOCs) form _______ at the base of cilia and flagella

basal bodies

Microtubule-organizing centers (MTOCs) bind to MT minus ends, allowing the MT plus ends to _________

extend outward

The ____________ is a MT-organizing center (MTOC)

centrosome

The centrosome contains ________ and many gammatubulin ring complexes (gTURC)

two centrioles

gammatubulin ring complexes (gTURC) binds ___________ subunits and promotes assembly of MTs

minus ends of tubulin

Growing microtubules show ____________

dynamic instability

Each MT grows & shrinks independently of its ____________

neighbor

Growing microtubules show dynamic instability and this is observed both in living cells and in experiments with ___________

purified proteins

Dynamic instability enables the cell to continuously monitor its __________

environment

Dynamic instability results from GTP hydrolysis

1. Addition of GTP-tubulin at the plus end of the MT forms a stable GTP cap

2. GTP hydrolysis destabilizes the MT

3. MTs with GDP-tubulin caps depolymerize rapidly

4. GDP-tubulin dimers must exchange their GDP for GTP before they can be added to a growing MT

Does the addition of a drug that inhibits hydrolysis of the GTP carried out by tubulin dimers promote microtubule growth?

Yes - Inhibition of GTP hydrolysis promotes the formation of a GTP cap. Microtubules with GTP caps will continually elongate.

Does the addition of a drug that inhibits exchange of GDP for GTP by tubulin dimers promote microtubule growth?

No - Tubulin dimers must exchange their GDP for GTP before being added to a microtubule plus end.

Does the addition of a drug that increases the affinity of GDP-tubulin dimers for other tubulin dimers promote microtubules growth?

Yes - Increasing the affinity of GDP-tubulin for other tubulin dimers will prevent the dissociation of GDP-tubulin dimers from microtubule plus ends in the event of loss of the GTP cap.

MTs organize the _________ of the cell

interior

MT capping proteins stabilize _________ ends (like a fish on the end of a fishing line)

plus

____________ of MTs can drive changes in cell shape. This also allows MTs to form long-distance tracks for transport

Selective stabilization

All cells need to transport materials from one region to another, especially _____________

neurons

A _____________ (minus ends in the cell body; plus ends pointing towards the axon terminals) provides tracks for transport

polarized MT array

Cargoes interact with ______________ , which move them along MTs

motor proteins

Motor proteins drive intracellular transport

1. Two distinct families of motor proteins interact with MTs

2. Kinesins walk to the MT plus end, dyneins walk to the minus end

3. Globular head domains (also called "motor domains") bind ATP & MT

4. Motor proteins use energy from ATP hydrolysis to drive movement

Motor protein tail domains interact with __________ cargoes

specific

Both kinesin and dynein are members of large gene families with _____________ & variable tail domains

conserved motor domains

The ____________ can interact with specific cargoes

variable tail domains

Defects in MTs & motor proteins are linked to ____________

nerve degeneration

Motor proteins organize organelles along MTs

1. Kinesin drives extension of the ER network along MT network

2. Dynein places Golgi close to the centrosome

Cilia & flagella contain stable MTs moved by ________

ciliary dynein

Cilia & flagella contain stable MTs moved by ciliary dynein slide

1. MT-based extensions of cell surface

2. Cilia move fluid or mucus over the surface of epithelia

3. Flagella move individual cells through fluid

4. Cilia beat in a whiplike fashion, flagella move like waves

5. Cilia and flagella share a conserved structure: "9+2" MT array

9+2 structure of cilia and flagella

1. 9 "outer doublet" MTs + 2 "central pair" MTs

2. Ciliary dynein is attached by its tail to one MT in each outer doublet, while its motor domain interacts with the adjacent MT

3. Arrangement of ciliary dyneins creates inner and outer dynein arms

4. Accessory proteins provide linkages (linking protein, radial spokes)

Dynein-driven MT sliding & bending in cilia and flagella

1. Dynein walks towards the minus end of MTs

2. Without linkages between neighboring MT doublets, MTs slide apart

3. With linkages, MTs bend

Kartagener's syndrome is a disease that results from defects in ____________

ciliary dyneins

Kartagener's syndrome leads to

1. Immotile sperm (sterility)

2. Chronic respiratory disease (immobile respiratory cilia)

3. 50% situs inversus (reversal of left/right body axis)

4. Left/right body axis is determined by motion of embryonic cilia

Actin filaments form many different _____________

structures

Actin filaments are thin and ________________

flexible

Actin filaments are ____________ to form stable bundles that support membranes (microvilli in the gut, stereocilia in the inner ear)

cross-linked

Actin filaments are also incorporated into ____________- (stress fibers, muscle)

contractile bundles

Actin can also form ________________ (filopodia, lamellipodia, contractile rings)

transient, dynamic arrays

______________ are the building blocks for actin filaments. This is analogous to the tubulin dimer

Actin monomers

Actin filaments are __________ nm in diameter

7

Actin filaments are structurally asymmetric and ____________

polar

Actin filaments have a plus end (fast assembly) and a ______________

minus end (slow assembly)

Actin monomers bind _____________

ATP