Question

a. How does regulated secretion differ from constitutive secretion?

b. What would be the effect of mutating the KDEL sequence of a resident ER protein (like BiP)? Would this effect be similar or different from that of mutating the KDEL receptor protein?

c.The pH of a compartment can be critical for association of a receptor and its cargo. How does the acidic pH of a late endosome result in different fates for the receptor and its cargo?

d. Why are carbohydrate groups of glycoproteins always exposed on the surface of the cell?

e.Compare and contrast the sorting of proteins to lysosomes to the packaging of proteins into regulated secretory granules such as those containing insulin.

f. How is a lysosomal protein targeted to a lysosome? What effect would be the addition of a lysosomal signal sequence have of subcellular localization of a protein that is normally cytosolic?  How would it affect localization of a protein that is normally secreted?

Answer 1

A: Upon synthesis and post-translational modification, a protein secreted from the cell. Nonetheless, the secretion of protein is modulated by constitutive or a regulated secretory pathway. Regulated secretory pathway involves packaging of synthesized proteins into a special subcellular structure called as secretory granules. These secretory granules stored in the cytoplasm and released only upon secretagogues stimulation. Whereas, a protein modulated by the constitutive secretory pathway, does not require secretagogues stimulation for its release. Constitutive secretory protein follows the constitutive secretion pattern.

B: KDEL is a conserved sequence located at C- terminus of mammals and plants protein. KDEL sequence act as a protein retention signal for the ER proteins. Additionally, KDEL sequence also facilitates the retrieval of accidental ER escaped protein. Mutation in   KDEL sequence will result in failure of retrieval of ER escaped protein by retrograde transport. Mutation in KDEL sequence of resident ER protein did not affect KDEL receptor protein. However, deletion of KDEL motif in ER resident protein would abolish the binding with KDEL receptor protein.