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The signal hypothesis is a fundamental concept in cell biology that explains how proteins are directed to specific cellular compartments, particularly the endoplasmic reticulum (ER), during their synthesis. According to this hypothesis, proteins destined for secretion, insertion into membranes, or residence within the endomembrane system contain an intrinsic signal sequence, typically located at their N-terminal region, which acts as a molecular “address label.” This sequence is recognized by specific cellular machinery that ensures the nascent protein reaches its correct destination. The hypothesis was first proposed based on experiments showing that secretory proteins initially carry extra amino acids at their N-terminus, which are subsequently cleaved once the protein enters the ER, _____ _______ ________ __________ ___ _______ _________ _________ ______ ________.
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