Signaling hypothesis

THE SIGNAL HYPOTHESIS EXPLAINS HOW POLYRIBOSOMES BIND TO THE ENDOPLASMIC RETICULUM... 

The signal hypothesis was proposed by Blobel and Sabatini pardy to explain the distinction between free and membrane-bound polyribosomes. They found that proteins synthesized on membrane-bound polyribosomes contained a peptide extension (signal peptide)... 

Blobel discovered the mechanism for protein translocation across the endoplasmic reticulum membrane—the signal hypothesis. 

Fig. 2. A simplified version of the signal hypothesis (see the text for details).

Martino G, Furlan R, BtambiUa E, Betgami A, Rufifini F, Gironi M, Pohani PL, Grimaldi LME, Comi G (2000) Cytokines and immunity in multiple sclerosis the dual signal hypothesis. J Neuroimmunol 109 3-9... 

Lingappa, V.R. and Blobel, G. (1980) Early events in the biosynthesis of secretory and membrane proteins the signal hypothesis. Recent Prog. Horm. Res. 36, 451 75. 

Fig. 1. The process of protein secretion according to the signal hypothesis.

The signal hypothesis postulates the existence of several proteins necessary for secretion. These include the components of the SRP, which is proposed to bind to the signal sequence and block further translation of the mRNA coding for the mature protein SRP receptor, or docking protein, which relieves the translation block imposed by the SRP ribophorins, which bind the ribosome to the ER membrane signal peptidase and signal-peptide peptidase, discussed above and other proteins, which form a pore or transport apparatus in the membrane. Some of these proteins, the SRP, SRP receptor, signal peptidase, and ribophorins, have been isolated from eukaryotic cell extracts and characterized. 

In eukaryotic systems, secretion of a protein across the ER requires the presence of a functional signal sequence and participation of SRP, the membrane and associated as yet undefined export apparatus, the SRP receptor, and a signal peptidase. Biochemical evidence derived from experiments in in vitro translocation systems generally supports the signal hypothesis (see Section II,C). 

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