Lakkaraju Asvin K K, Mary Camille, Scherrer Anne, Johnson Arthur E, Strub Katharina
Département de biologie cellulaire, Université de Genève, Sciences III, 1211 Geneva, Switzerland.
Cell. 2008 May 2;133(3):440-51. doi: 10.1016/j.cell.2008.02.049.
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.
信号识别颗粒（SRP）对于将新生肽链靶向内质网至关重要，并且它会在无细胞翻译系统中延迟新生肽链的延伸。然而，该功能的重要性仍不清楚。我们发现，由于信号识别颗粒受体（SR）的浓度限制了速率，有效的蛋白质转运到内质网与正常的细胞翻译速率不相容。我们通过表达缺乏延伸阻滞功能的该蛋白突变体来补充缺乏SRP14的哺乳动物细胞。缺乏延迟会导致前体蛋白靶向效率低下，从而导致分泌缺陷、内膜中蛋白质的消耗以及细胞生长减少。通过降低细胞蛋白质合成速率或增加SR表达可以逆转这些有害影响。因此，信号识别颗粒确保新生肽链在由SR决定的靶向时间窗口内保持转运能力。由于信号识别颗粒与信号序列的亲和力不同，这种延迟也可能调节哪些蛋白质被优先靶向。
