Neuroscience
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Section I:
Cellular and Molecular Neurobiology



10. Transport and the Molecular Mechanism of Secretion
Part 2 of 5

Jack C. Waymire, Ph.D.

Synthesis of Vesicles and Proteins

Perinuclear Cisterna Rough Endoplasmic Reticulum Golgi

Figure 10.2

Diagrammatic representation of the organelles involved in vesicle

The cycle of neurotransmitter vesicles begins in the ER where the proteins that make up the vesicles are synthesized. Vesicle biosynthesis continues as the proteins migrate through the smooth ER and the Golgi apparatus to eventually emerge to be transported to the nerve ending. The outer layer of the nuclear envelope is contiguous with the endoplasmic reticulum, which is in turn contiguous with the Golgi apparatus.

To view the processes involved in the biosynthesis of vesicular proteins, click on one of these structures in Figure 10.2.

Perinuclear Cisternae and Ribosomal Protein Synthesis

As shown in Figure 10.3, after the mRNA is transcribed from the DNA in the nucleus, it migrates through pores in the nuclear envelope called the perinuclear cisternae (label (A) in Figure 10.3). As the mRNA reaches the cytoplasm it encounters free ribosomes, labeled (B). This is the site of cytoplasmic protein synthesis. Here, triplet nucleotide combinations, called codons, translate the mRNA into protein through a mechanism where ribosomes read off the protein sequence encoded in the mRNA. As ribosomes move along the mRNA template amino acids are added and the protein synthesized. Because most mRNA molecules are longer than a ribosome, many ribosomes can read the codons of a single molecule of RNA.

Click "B" in the graphic at right for animation of cytoplasmic protein synthesis.

Proteins that are destined to be associated with membrane structures, such as neurotransmitter vesicles or the plasmalemma, are synthesized on ribosomes within the endoplasmic reticulum. Recall that the presence of ribosomes defines this part of the endoplasmic reticulum as rough endoplasmic reticulum.

Animation of integral membrane protein synthesis Animation of cytoplasmic protein synthesis

Figure 10.3

Diagrammatic representation of the sites of cellular protein synthesis

Click (B), in graphic above, for animation of cytoplasmic protein synthesis.

Click (C), in graphic above, for an animation of integral membrane protein synthesis)

In (C) of Figure 10.3, the polypeptide (protein) being synthesized has no signal peptide. Consequently, this protein will become a non-membrane bound (soluble) protein that resides within lumen of vesicles. While in the lumen, the protein undergoes further processing as it proceeds through the smooth ER, Golgi apparatus, and the secretory vesicle as mature secretory proteins are formed.

In (D) of Figure 10.3, a signal peptide is a part of the polypeptide being synthesized (this is signified in the figure by the fact that the peptide is anchored in the ribosomal membrane). Consequently, this protein will be an integral membrane protein. As the ribosome moves along the mRNA template, amino acids are added. The signal peptide inserts in the membrane of the endoplasmic reticulum and maintains the protein's association with membrane. This will ensure that the protein will associate with a vesicular structure, such as a neurotransmitter storage vesicle. Shows the protein synthesis from ribosomes in the rough ER to synthesize membrane bound protein.

Click "C' in Figure 10.3 for an animation of integral membrane protein synthesis.

Return to Synthesis of Vesicles graphic (Figure 10.2) at top of page.

Rough Endoplasmic Reticulum

Figure 10.4

Diagram of the budding of vesicle from the SER and fusion with the Golgi Apparatus

 Figures 10.4 illustrates the movement of the secretory vesicles through the rough and the smooth ER. The smooth ER extends from the RER and serves as a site for lipid biosynthesis for the production of endosomes, lysosomes and plasma membrane as well as for the neurotransmitter vesicles. New membrane protein that begins its synthesis in the RER continues in the SER where pieces of the SER bud off to form transport vesicles that shuttle to the Golgi apparatus with their contents.

Return to Synthesis of Vesicles graphic (Figure 10.2) at top of page.

Golgi

As shown in Figure 10.5, in the Golgi apparatus the vesicles fuse to form the outermost of the Golgi apparatus cisternae stacks. Each cisterna migrates in a stepwise fashion through the Golgi apparatus toward the concave surface. During this migration, proteins become more concentrated and undergo various types of biochemical modification to produce mature functional proteins. These modifications include phosphorylation, glycosylation, proteolysis and addition of fatty acids, as well as others. The migration proceeds from the cis face close to the SER to the concave trans face. Upon reaching the concave face the cisternae round up into small vacuoles, then coalesce to form a larger condensing vacuole. The condensing vacuoles then give rise to a number of dense spherical transport vesicles. These vesicles bud off and are transported to the various destinations within the neuron where they become cell membrane, lysosomes, endosomes or neurotransmitter vesicles.


Figure 10.5

Diagram of the budding of vesicle from the Golgi Apparatus

Return to Synthesis of Vesicles graphic (Figure 10.2) at top of page.



Contact the author(s) at: nba_course@uth.tmc.edu
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