Lecture 27 - Molecular and Cell Biology

From ER to Golgi:

transport in vesicles via bulk flow (no signal necessary)
instead signal sequence necessary for retention in ER (most commonly Lys-Asp-Glu-Leu or KDEL at carboxyl terminus, KDEL stands for the 4 amino acids in their single letter code)
membrane-bound proteins are directly retained, soluble proteins are retrieved from Golgi

In Golgi:

• arrival of vesicles at cis Golgi network, sorting for recycling to ER or further transport to Golgi stack
  
• in Golgi stack: further protein processing
  • via addition of simple oligosaccharides to serines or threonines that lie in a specific sequence context (O-linked glycosylation, because addition at -OH group of serine or threonine).
    
  • Some N-linked oligosaccharides are modified to carry mannose-6-phosphate at their ends ---- targets proteins to lysosome. Specific signal in protein provides information for necessary mannose-6-phosphate modification.
    
  • Secreted and plasma membrane proteins extensively modified at their N-linked oligosaccharides when traveling from cisterna to cisterna (but depends on modifying enzymes present in Golgi stack and accessibility of oligosaccharide rather than on a specific signal sequence in the protein)
  
  
• in trans Golgi network: final sorting!
  • If no specific signal: in vesicles with bulk flow to plasma membrane.
    
  • Specific sequence necessary for retention in Golgi.
    
  • Specific sugar signal (mannose-6-phosphate) for lysosome targeting.
  
  

If proteins synthesized on free ribosomes
folded and processed in cytosol
transported to

• nucleus: specific amino acid sequence called nuclear localization signal that direct their transport through the nuclear pore complex (signal is internal sequence, is not cleaved)
  
• mitochondrion and chloroplast: signal sequence at amino terminal end (cleaved following import)

All cells receive and respond to signals from their surroundings.

The signals may be environmental factors like light or they may be signals produced by other cells.

Signals from other cells are especially important in complex multicellular organisms, like humans, where they integrate and coordinate the functions of the individual cells for the benefit of the whole organism.

In complex multicellular organisms cell-cell signaling can be divided into 3 general categories depending on the distance over which the signal is transmitted: (Fig. 13.1)

• endocrine signaling: the signal molecule is secreted by specialized endocrine cells, carried over far distances with the circulatory system, and finally is perceived by target cells far away from the signal-producing cells. Such signaling molecules are called hormones, per definition signal molecules that act over great distances.
  
• paracrine signaling: the signal molecule acts locally on neighboring cells. The signal molecule might not even be released into the extracellular fluid by the signal-producing cell but rather expressed on its surface (direct cell-to-cell signaling).
  
• autocrine signaling: the signaling molecule acts on the signal-producing cell itself inducing it to respond.

Another prerequisit for response to a signal is the ability of the activated receptor (the receptor that has bound a signal molecule) to induce some kind of intracellular reaction that leads to the response behavior.

Many receptors are located at the cell surface, but some are localized inside the cell (intracellular).

An example for intracellular receptors are the steroid hormone receptors. They respond to steroid hormones like the sex hormone estrogen but there are also many other sex or non-sex steroid hormones. By the way the name steroid hormones already indicates endocrine signaling.

Because steroid hormones are small, hydrophobic molecules they can cross the plasma membrane which allows them to bind to their intracellular receptors.

All steroid hormone receptors act as transcription factors therefore directly influencing gene transcription. For example the estrogen receptor cannot bind DNA in the absence of the hormone. Binding of estrogen induces a conformational change in the receptor allowing it to bind to specific regulatory DNA sequences and therefore to activate transcription of certain genes as a response.

Comments or questions should be directed to Cheryl.Davis@wku.edu
Last Modified: May 8, 1998
All contents copyright (C) 1997.
Western Kentucky University.