Proteins which are secreted by cells




















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PLoS Negl. MacLean, L. Cargo-bearing vesicles pinch off of one set of membranes and travel along microtubule tracks to the next set of membranes, where they fuse with these structures. Trafficking occurs in both directions; the forward direction takes vesicles from the site of synthesis to the Golgi apparatus and next to a cell's lysosomes or plasma membrane. Vesicles that have released their cargo return via the reverse direction.

The proteins that are synthesized in the ER have, as part of their amino acid sequence, a signal that directs them where to go, much like an address directs a letter to its destination.

Soluble proteins are carried in the lumens of vesicles. Any proteins that are destined for a lysosome are delivered to the lysosome interior when the vesicle that carries them fuses with the lysosomal membrane and joins its contents.

In contrast, the proteins that will be secreted by a cell, such as insulin and EPO, are held in storage vesicles. When signaled by the cell, these vesicles fuse with the plasma membrane and release their contents into the extracellular space.

The Golgi apparatus functions as a molecular assembly line in which membrane proteins undergo extensive post-translational modification. Many Golgi reactions involve the addition of sugar residues to membrane proteins and secreted proteins. The carbohydrates that the Golgi attaches to membrane proteins are often quite complex, and their synthesis requires multiple steps. In electron micrographs, the Golgi apparatus looks like a set of flattened sacs. Vesicles that bud off from the ER fuse with the closest Golgi membranes, called the cis-Golgi.

Molecules then travel through the Golgi apparatus via vesicle transport until they reach the end of the assembly line at the farthest sacs from the ER — called the trans-Golgi. At each workstation along the assembly line, Golgi enzymes catalyze distinct reactions. Later, as vesicles of membrane lipids and proteins bud off from the trans-Golgi, they are directed to their appropriate destinations — either lysosomes, storage vesicles, or the plasma membrane Figure 2.

Figure 2: Membrane transport into and out of the cell Transport of molecules within a cell and out of the cell requires a complex endomembrane system. Endocytosis occurs when the cell membrane engulfs particles dark blue outside the cell, draws the contents in, and forms an intracellular vesicle called an endosome. This vesicle travels through the cell, and its contents are digested as it merges with vesicles containing enzymes from the Golgi.

The vesicle is then known as a lysosome when its contents have been digested by the cell. Exocystosis is the process of membrane transport that releases cellular contents outside of the cell. Here, a transport vesicle from the Golgi or elsewhere in the cell merges its membrane with the plasma membrane and releases its contents.

In this way, membranes are continually recycled and reused for different purposes throughout the cell. Membrane transport also occurs between the endoplasmic reticulum and the Golgi. COPI also forms vesicles for intra-Golgi transport. Clathrin blue forms multiple complexes based on its association with different adaptor proteins APs. Clathrin that is associated with AP1 and AP3 forms vesicles for transport from the trans-Golgi network to the later endosomal compartments, and also for transport that emanates from the early endosomal compartments.

Clathrin that is associated with AP2 forms vesicles from the plasma membrane that transport to the early endosomes. The evolving understanding of COPI vesicle formation.

Nature Reviews Molecular Cell Biology 10, All rights reserved. Figure Detail Lysosomes break down macromolecules into their constituent parts, which are then recycled. These membrane-bound organelles contain a variety of enzymes called hydrolases that can digest proteins, nucleic acids, lipids, and complex sugars.

The lumen of a lysosome is more acidic than the cytoplasm. This environment activates the hydrolases and confines their destructive work to the lysosome.



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