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C2-09 Microtubule Motors and Cell Motility
Even More Cell Stuff
18
Biochemistry
Professional
09/23/2010

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Cards

Term

 

 

 

Minus ends of microtubules 

Definition

are usually embedded in microtubule organizing center (MTOC) - Centriole/centrosome/ basal body / spindle pole body

Term

 

 

Like actin, rate limiting step in microtubule formation........

Definition

 

 

 

NUCLEATION!

Term

 

 

 

Not all Microtubules have (-) ends in MTOC

(Exceptions)

Definition

fungi have spindle pole body imbedded in nuclear membrane but no centrioles
plant cells and vertebrate oocytes have no centrosomes

Term

 

 

 

Stable Microtubules

Definition

Cilia and flagella
Adult axon microtubules
Marginal microtubule bands in RBCs

Term

 

 

 

Dynamic Microtubules

Definition

Spindle microtubules
Cytoplasmic microtubules 

Term

 

 

Dynamic Properties of Microtubules

Definition

Guanine nucleotide at + end of microtubule.
Only GTP-tubulin has a strong tendency to form microtubules.
After GTP-tub polymerizes, the GTP gradually hydrolyzes to GDP.  Microtubules capped with GDP rapidly depolymerize.
Microtubule binding proteins can contribute to growth and shrinkage.
Drugs
Colchicine, vinblastine, nocodozole (destabilize microtubules)

Term




Structural difference between GTP-tubulin and GDP-tubulin

Definition

-probably responsible for the rapid depolymerization of microtubules with GDP-cap

Term



Does dynamic instability serve any purpose?

Definition

1) Organizing principle for cell morphogenesis

2)Capture of chromosomes in mitotic prophase

3) Propulsive Force

Term




Cilia and Flagella

Definition

Have nine microtubule doublets arranged in a circle
Develop from a basal body/centriole with nine microtubule triplets.
Classified into 8 groups but all have either either 9+2 or 9+0 arrangement of microtubules.
Mobile or non-mobile

Term

 

 

 

Mobile Cilia

Definition

9+2 arrangement of microtubules

Present on ciliated epithelia and sperm use dynein motor for movement

Term

 

 

Non-Mobile Cilia

Definition

mostly 9+0 arrangement of microtubules

present on the apical surface of most no-proliferating cells.

often have sensory role.

Term



physiological role of cilia

Definition

Immotile-cilia syndrome.
Kartagene Syndrome
Due to mutation in dynein motor heavy chain

patents present with:
respiratory problems (immotile respiratory cilia)
sterility (immotile sperm)
situs inversus:

Term

 

 

 

primary cilia as sensory organelles

Definition

Autosomal dominant polycystic kidney disease (PKD)
Most common single gene genetic disease, affecting 1/400-1/500 adults. Caused by development of renal cysts. Patients often present with hypertension, pain, or urinary tract infections. Dominant mutations in two genes, PKD1 and PKD2 are responsible for most of the cases.
Current Treatment
Kidney transplantation and or dialysis (8-10% of dialysis patients have PDK)
Hypothesis:
primary cilia in renal epithelium monitor fluid flow through renal tubules and regulate cell proliferation via calcium signaling.  Loss of cilia function blocks the signaling pathway leading to cell proliferation and cyst formation.
Treatment
Several drugs are in clinical trials - Vasopressin receptor antagonists and the mTor inhibitor, rapamycin

Term

 

 

 

Cytoplasmic dynein

Definition

Minus end motor (moves to minus end of microtubule -retrograde movement)
Directs vesicle movement along microtubules towards microtubule organizing center - retrograde movement. Usually associated with the dynactin complex
Also has role in mitotic spindle and chromosome segregation   

Term

 

 

 

Kinesin

Definition

Plus end motor (moves to plus end of microtubule -anteriograde movement)
Directs vesicle movement along microtubules away from  microtubule organizing center - anteriograde movement
large collection of kinesin-like proteins   

Term

 

 

 

Physiological roles for kinesin-related proteins

Definition

assembly and function of mitotic and meiotic spindle.
membrane movement
assembly of cilia
signaling
transport of RNAs and proteins

Term

 

 

Communication between actin and microtubules

Definition

Ex.
cell migration - growing microtubule ends traffic actin regulators
myosin V-dependent spindle orientation in yeast
vesicle trafficking
immunological synapse

Term

 

 

 

 Range Movement in Cells

Definition

Long range movement- microtubule motors

Short range movement- actin motors

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