Updated: 4/6/2021

Microtubules

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Overview
  • IntroductioThis illustration highlights the basic components and structure of a microtubule. Microtubules are composed of alpha and beta tubulin proteins. These tubulin dimers form a protofilament, which then associate laterally with adjacent protofilaments (usually 13) to yield a microtubule. Kinesin and Dynein are involved in anterograde and retrograde transport, respectively. n
    • cellular structural protein with a hollow tubular structure
  • Structure
    • composed of polymerized dimers of α- and β-tubulin
      • each dimer has 2 GTP molecules bound
    • constant assembly (slow) and disassembly (fast)
      • clinical importance
        • Chédiak–Higashi syndrome (CHS)
          • etiology
            • a disease caused by a microtubule polymerization defect
          • resulting in decreased chemotaxis, degranulation, phagocytosis
          • AR inheritance
          • presentation
            • recurrent pyogenic infections
              • particularly S. aureus
            • partial albinism
            • peripheral neuropathy
  • Function
    • component of many important cellular structures
      • cilia
        • 9+2 arrangement of microtubules
        • axonemal dynein
          • ATPase that attaches the peripheral 9 doublets
          • causes bending of cilium by binding differentially to doublets
        • also forms the core of flagella
        • clinical importance
          • Kartagener syndrome  
            • immotile cilia disease
            • cause
              • dynein arm defect 
            • presentation
              • male and female infertility
                • sperm are immotile (no functional flagellar tail)
                • Fallopian tubes cannot sweep egg and sperm towards each other 
              • bronchiectasis
              • recurrent sinusitis
                • mucus with bacteria and particles cannot be removed
              • associated with situs inversus
      • mitotic spindles
      • molecular motor proteins 
        • mediates intracellular transport
        • 2 types
          • kinesin 
            • cell center → periphery
            • anterograde to microtubule
            • e.g. transports neurotransmitter vesicles down axon towards synapse
            • also transports Herpes zoster virus particles from the dorsal root ganglion during reactivation as shingles 
          • dynein 
            • periphery → cell center
            • retrograde to microtubule
            • e.g. lipid transport from synapse back to Golgi apparatus
  • Pharmacologic importance
    • mebendazole
      • class: antihelminthic
      • mechanism of action
        • microtubule synthesis in worms
    • griseofulvin
      • class: antifungal
      • mechanism of action
        • deposits in new keratin and disrupts microtubule polymerization
      • uses
        • active against dermatophytes only
    • vincristine/vinblastine 
      • class: anti-cancer
      • mechanism of action
        • ↓ microtubule polymerization
          • inhibits mitosis
      • side effects
        • peripheral neuritis
        • areflexia
        • myelosuppression
    • paclitaxel (taxol)
      • class: anti-breast cancer
      • mechanism
        • ↑ stability of microtubule and does not allow disassembly
          • inhibits mitosis
    • colchicine 
      • class: anti-gout
      • mechanism of action
        • binds free tubulin
        • ↓ microtubule polymerization
          • inhibits leukocyte/granulocyte migration

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Questions (8)
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(M1.BC.15.74) A 52-year-old man awakens in the middle of the night with excruciating pain in his right great toe. He reports that even the touch of the bed sheet was unbearably painful. His right foot is shown in figure A. He is treated with colchicine. Which of the following describes the mechanism of colchicine? Tested Concept

QID: 106643
FIGURES:
1

Inhibition of xanthine oxidase

17%

(38/225)

2

Inhibition of reabsorption of uric acid in proximal convoluted tubule

12%

(27/225)

3

Nonselective inhibition of cyclooxygenase (COX) 1 and 2

5%

(12/225)

4

Binds to glucocorticoid receptor

0%

(0/225)

5

Decreases microtubule polymerization

64%

(145/225)

M 1 D

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(M1.BC.15.74) A 29-year-old male presents with his wife to his primary care physician with a complaint of infertility. His medical history is significant for recurrent respiratory infections since he was a child. Semenalyis is ordered and reveals significantly reduced sperm motility. To confirm the suspected diagnosis, the physician orders a chest radiograph, which is shown in Figure A. Which of the following is the cause of this patient's condition? Tested Concept

QID: 106657
FIGURES:
1

Microtubule polymerization defect

4%

(1/23)

2

Kinesin protein mutation

13%

(3/23)

3

Sphingomyelinase deficiency

0%

(0/23)

4

Dynein arm defect

78%

(18/23)

5

LFA-1 integrin (CD18) defect

0%

(0/23)

M 1 D

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(M1.BC.15.70) In large neurons the nucleus can be found a large distance away from the terminal end of its axon. The body has a complex system of intracellular transporters that are able to carry essential proteins from the nucleus to the distal edge of the cell and back. Which of the following proteins are essential for this function? Tested Concept

QID: 106481
1

Kinesin, Troponin

8%

(2/26)

2

Dynein, Kinesin

92%

(24/26)

3

Actin, Dynein

0%

(0/26)

4

Myosin, Kinesin

0%

(0/26)

5

Glucose, Actin

0%

(0/26)

M 1 D

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(M1.BC.13.32) Which of the following cells in the body depends on dynein for its unique functioning? Tested Concept

QID: 101696
1

Lower esophageal mucosal cell

2%

(7/308)

2

Fallopian tube mucosal cell

77%

(236/308)

3

Small intestinal mucosal cell

4%

(11/308)

4

Skeletal muscle cell

13%

(39/308)

5

Adipocyte

2%

(7/308)

M 1 E

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