Cytoskeleton and ECM

Question 1

Within the kinesin family, the MOTOR domain is highly __________. The tails are __________, enabling them to attach to different cargos and targets.

Answer 1

(Conserved; variable)

Question 2

Kinesin

Type of motor and direction

Answer 2

Positive + end motor has it move towards PERIPHERY, GTPase activity means it walks on MICROTUBULES

Question 3

Dynein

Motor type, filament, direction, disease

Answer 3

Negative - end directed motor, takes cargo towards NUCLEUS, walks on MICROTUBULES
Also associated with cilia in 9+2 arrangement for movement; defect: Primary Cilia Dyskinesia

Question 4

Myosin

Motor type, filament association, direction, application

Answer 4

Positive + end directed, associated with ACTIN filaments, seen in muscle contraction (Myosin II) and in melanosomes for melanin transport (Myosin Va).
Defect: Griscelli Type I

Question 5

Intermediate filaments
(Polarity, polymer structure, found in)

Answer 5

Not polar, have a 2-chain coiled coil structure, seen in Keratin, neurofilaments and nuclear lamina

Question 6

Microtubules

Polarity, structure, assembly, where found

Answer 6

POLAR, 13 protofilament hollow polymer structure. Need a GTP-cap to stabilize and polymerize to (+) end, originate from basal bodies or centrosomes (gamma tubulin core). Found in spindle fibers, axons and near secretory vesicles.

Question 7

Actin Filaments

Polarity, Structure, Assembly, rate-limiting step

Answer 7

POLAR, helical filament with a (+) barbed end that grows FASTER than the (-) blunt end. Assembles via a “nucleation” rate limiting step, where ATP hydrolysis forms G-actin to polymerize.

Question 8

Describe the Myosin Classes

I, II, V

Answer 8

Myosin I - single headed, tail binds to PM, tip is at (+) end of MICROVILLI
Myosin II - bipolar filaments found in MUSCLE for contraction
Myosin V - carries cargo; attached to VESICLES for transport

Question 9

What is Arp2/3 complex associated with?

Answer 9

Wound healing,
Neutrophil movement,
Metastasis,
Clathrin Endocytosis

Question 10

What is a primary cilium?

Answer 10

A single cilia per cell that functions in signaling. It is not motile as it LACKS the 2 microtubules in the center and does not have dynein

Question 11

Describe Integrins.

Answer 11

Beta subunits dimers use a RGD sequence to bind substrate such as actin cytoskeleton to initiate signaling complexes; regulate (FAK) focal adhesion kinases to enable signaling pathways (integrins are regulated themselves too)

Question 12

Classes of Integrins

Beta 1,2,3,4: where found, functions, related diseases

Answer 12

Beta1 - UBIQUITOUS (commonplace); binds fibronectin and laminin
Beta2 - enables WBCs (in leukocyte extravasation) to bind counter-receptors;
*Leukocyte adhesion deficiency: slippery WBCs don’t bind endothelium, bad immune system
Beta3 - enables PLATELETS to bind fibrinogen in clotting cascade
*Glanzmann’s disease: platelets don’t bind fibrinogen, no clotting
Beta4 - HEMIDESMISOMES; a6b4 component anchors intermediate filaments, binds fibrinogen

Question 13

Describe Glycosaminoglycans (GAGs).

Answer 13

Complex sugars that bind water, negatively charged at body pH; alternating chains of (NAcGal and NacGlu) + Uronic Acid

Question 14

Describe Elastin Fibers

Related disease

Answer 14

Known for resilience in ECM; stretch/recoil CT.
High concentration in aorta CT, lung and skin.
Composed of cross-linked elastin and fibrillin and specially stained in LM.
*Marfan Syndrome: missense mutation in fibrillin 1 gene; elongated limbs, high risk of aortic rupture

Question 15

Describe Proteoglycans.

Definition, Types and where found

Answer 15

A bunch of GAGs attached to a core protein.
Cartilage Proteoglycan - aka aggrecan; hyaluronan backbone with many branches, provide mechanical support
“Aggregates cartilage”
Perlecan - found in basal lamina; function in filtering and structure
“Percolate the ECM”
Syndecan(1) - located in fibroblast; role in signaling pathways
“Send a can of signals”

Question 16

Describe Syndecan.

Answer 16

This Proteoglycan is a type of membrane glycoprotein commonly located in fibroblasts and epithelial cells. It functions in signaling pathways.
“Send-a-can of signals” (Interacts with ECM to do this)

Question 17

Describe Perlecan.

Answer 17

This proteoglycan is found in lamina densa of the basement membrane. It functions for structure and filtration.
“Percolates the basal lamina” (like a mesh of porous clay)

Question 18

Describe Aggrecan.

Answer 18

This HUGE proteoglycan provides mechanical support in cartilage. It’s composed of a hyaluronan backbone, branches of chondroitin sulfate and sub-branches of keratin sulfate.
“Aggregates in cartilage”

Question 19

Describe the 3 layers of the basement membrane.

Answer 19

Lamina lucida - EPITHELIUM GLUE;
Collagen 17 (in anchoring filaments)
Lamina densa - COMPLEX NETWORK; Collagen 4 (anchoring plaques)
“Collagen 4 in da floor!”
Lamina reticularis - ANCHOR TO STROMA;
Collagen 3 (reticular fibers that anchor epithelium to CT)

Question 20

Beta 1 Integrin

Answer 20

UBIQUITOUS (commonplace); binds fibronectin and laminin

Question 21

Beta 2 Integrin

Answer 21

enables WBCs (in leukocyte extravasation) to bind counter-receptors; 
*Leukocyte adhesion deficiency: slippery WBCs don't bind endothelium, bad immune system

Question 22

Beta 3 Integrins

Answer 22

enables PLATELETS to bind fibrinogen in clotting cascade

*Glanzmann’s disease: platelets don’t bind fibrinogen, no clotting

Question 23

Beta 4 Integrins

Answer 23

HEMIDESMISOMES; a6b4 component anchors intermediate filaments, binds fibrinogen