SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites.
SRP is essential for targeting nascent chains to the endoplasmic reticulum, and it delays nascent chain elongation in cell-free translation systems. However, the significance of this function has remained unclear. We show that efficient protein translocation into the ER is incompatible with normal cellular translation rates due to rate-limiting concentrations of SRP receptor (SR). We complemented mammalian cells depleted of SRP14 by expressing mutant versions of the protein lacking the elongation arrest function. The absence of a delay caused inefficient targeting of preproteins leading to defects in secretion, depletion of proteins in the endogenous membranes, and reduced cell growth. The detrimental effects were reversed by either reducing the cellular protein synthesis rate or increasing SR expression. SRP therefore ensures that nascent chains remain translocation competent during the targeting time window dictated by SR. Since SRP-signal sequence affinities vary, the delay may also regulate which proteins are preferentially targeted.
Lakkaraju
Asvin K K
AK
Département de biologie cellulaire, Université de Genève, Sciences III, 1211 Geneva, Switzerland.
Mary
Camille
C
Scherrer
Anne
A
Johnson
Arthur E
AE
Strub
Katharina
K
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D002474:Cell-Free System; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D018271:Signal Recognition Particle / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D011500:Protein Synthesis Inhibitors; C490326:SRP14 protein, human; D018271:Signal Recognition Particle; D049452:Green Fluorescent Proteins