Neuroscience
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Section I:
Cellular and Molecular Neurobiology



10. Transport and the Molecular Mechanism of Secretion
Part 5 of 5

Jack C. Waymire, Ph.D.

Vesicle Recapture

Although the source of vesicles for neurotransmitter secretion comes from biosynthesis in the Golgi apparatus at the cell body, evidence indicates that local re-synthesis of synaptic vesicle is an important aspect of neurotransmitter secretion. Figures 10.9 and 10.10 provides two schematic summaries of how vesicles are locally reused. Both utilize the recapture of vesicle membrane from the nerve ending. In one, vesicles bud off the plasma membrane through the formation of pits that migrate directly to become a neurotransmitter vesicle as soon as it can be refilled with neurotransmitter through the neurotransmitter uptake process. This is shown in Figure 10.9. This mechanism is referred to as the "kiss and run" hypothesis. The second mechanism involves the formation of clathrin coated pits to recapture vesicle membrane, and the vesicles cycle through the endosomal compartment in the nerve ending before becoming functional synaptic vesicles. The vesicles then bud off the endosome to form the neurotransmitter vesicle. This is shown in Figure 10.10. It is believed that both mechanisms can exist in the same nerve ending or only one of the two can be present. Both are important in that they recover vesicle protein to permit a plentiful supply for synaptic transmission. This mechanism also prevents the enlargement of the nerve ending that would occur if vesicle membrane were not recaptured. No matter which mechanism is involved, the supply and resupply of vesicles can only keep pace with a high rate of synaptic transmission for a few minutes.

Figure 10.9


Figure 10.10

Representation of two mechanisms proposed to recapture vesicle membrane during neurotransmitter secretion.

Retrograde Axoplasmic Transport

Figure 10.11

Retrograde axoplasmic transport mediated by dynein association with microtubules

Eventually the proteins utilized for synaptic transmission in the nerve ending are targeted and returned to the cell body of the neuron to be recycled to make new protein and vesicles. The proteins are returned to the soma through a retrograde axoplasmic transport that is analogous to anterograde transport but uses a different motor protein, dynein. Transport is mediated by the interaction of dynein with microtubules and proceeds at a rate somewhat slower than that of fast anterograde transport (0.2-1 cm per day). In addition to returning proteins to the soma, retrograde transport serves as a means of communication between the nerve endings and the cell soma. This is a mechanism to transport signaling molecules to regulate the development and maintenance of axonal contacts with postsynaptic cells.

Figure 10.12

Figure 10.12 shows a summary of retrograde and anterograde axoplasmic transport. It shows the motor proteins, kinesin and dynein, mediating the movement of vesicles and mitochondria anterogradely and vesicles retrogradely along microtubules. The animation shows the motor proteins as a part of the organelle that is transported. The other possible relationship between the motor protein and microtubules is that the motor proteins are a part of the microtubule and pass the vesicles along the microtubule.

 

Test Your Knowledge

Which of the following processes dictate the amount of neurotransmitter released from a nerve ending on a short-term, minute-to-minute, basis? (NOTE: there is more than one correct answer.)

A. Neurotransmitter synthesis

B. Vesicle synthesis in the cell soma

C. Vesicle recycling in the nerve ending

D. Axoplasmic transport

E. Calcium availability

Which of the following processes dictate the amount of neurotransmitter released from a nerve ending on a short-term, minute-to-minute, basis? (NOTE: there is more than one correct answer.)

A. Neurotransmitter synthesis This answer is CORRECT!

Because there is only sufficient neurotransmitter available in a nerve ending for a minute or so of continued released, the biosynthesis of new neurotransmitter to fill the recycled neurotransmitter vesicle is necessary for continued availability of neurotransmitter for release.

B. Vesicle synthesis in the cell soma

C. Vesicle recycling in the nerve ending

D. Axoplasmic transport

E. Calcium availability

Which of the following processes dictate the amount of neurotransmitter released from a nerve ending on a short-term, minute-to-minute, basis? (NOTE: there is more than one correct answer.)

A. Neurotransmitter synthesis

B. Vesicle synthesis in the cell soma This answer is INCORRECT.

The synthesis of vesicles in the cell body is necessary to supply the nerve ending with vesicles for neurotransmission on a long-term basis. On a short-term basis vesicle membrane undergoes recapture and vesicles are locally reconstituted to be used for continued neurotransmission.

C. Vesicle recycling in the nerve ending

D. Axoplasmic transport

E. Calcium availability

Which of the following processes dictate the amount of neurotransmitter released from a nerve ending on a short-term, minute-to-minute, basis? (NOTE: there is more than one correct answer.)

A. Neurotransmitter synthesis

B. Vesicle synthesis in the cell soma

C. Vesicle recycling in the nerve ending This answer is CORRECT!

Vesicles are recycled locally at the nerve ending. The recycling may or may not involve fusion with the endosmose.

D. Axoplasmic transport

E. Calcium availability

Which of the following processes dictate the amount of neurotransmitter released from a nerve ending on a short-term, minute-to-minute, basis? (NOTE: there is more than one correct answer.)

A. Neurotransmitter synthesis

B. Vesicle synthesis in the cell soma

C. Vesicle recycling in the nerve ending

D. Axoplasmic transport This answer is INCORRECT.

The delivery of new vesicles to the nerve ending via axoplasmic transport provides the vesicles necessary for neurotransmission on a long term basis. Vesicle recycling within the nerve ending is the mechanism that provides vesicles for neurotransmission on a short-term basis.

E. Calcium availability

Which of the following processes dictate the amount of neurotransmitter released from a nerve ending on a short-term, minute-to-minute, basis? (NOTE: there is more than one correct answer.)

A. Neurotransmitter synthesis

B. Vesicle synthesis in the cell soma

C. Vesicle recycling in the nerve ending

D. Axoplasmic transport

E. Calcium availability This answer is CORRECT!

Increase in calcium level within the nerve ending, either through influx of external calcium or release of internal calcium, is instrumental in the initiation of vesicle mobilization and exocytosis. In some types of neurons (acetylcholine- and catecholamine-releasing neurons) calcium level also regulates neurotransmitter biosynthesis.

 

 

 

 

 

 

 

 

 


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