Université de Franche-Comté, Laboratoire de Biochimie, EA3922, Estrogènes, Expression Génique et Pathologies du Système Nerveux Central, IFR133, U.F.R. Sciences et Techniques, Besançon, France.
Autophagy. 2010 May;6(4):495-505. doi: 10.4161/auto.6.4.11819. Epub 2010 May 16.
Gabarapl1 (gec1) was first described as an estrogen regulated gene which shares a high sequence homology with the gabarap gene. We previously demonstrated that GABARAPL1, like GABARAP, interacts with the GABAA receptor and tubulin and promotes tubulin polymerization. Previous work has demonstrated that the GABARAP family members (GABARAP, LC3, GATE-16 and Atg8) are not only involved in the transport of proteins or vesicles but are also implicated in various mechanisms such as autophagy, cell death, cell proliferation and tumor progression. We therefore asked whether GABARAPL1 might also play a role in autophagy. First, we showed that GABARAPL1 is cleaved at glycine 116, a residue which is conserved in other members of the family. We also demonstrated that GABARAPL1 is linked to phospholipids, delipidated by Atg4B, associated with intracellular membranes and accumulated in intracellular vesicles after inhibition of lysosomal activity. Finally, we showed that GABARAPL1 partially colocalizes with LC3 or Lysotracker green in intracellular vesicles. Taken together, our results demonstrate that GABARAPL1 associates with autophagic vesicles.
Gabarapl1（gec1）最初被描述为一种雌激素调节基因，与 gabarap 基因具有高度序列同源性。我们之前证明，GABARAPL1 与 GABARAP 一样，与 GABA A 受体和微管蛋白相互作用，并促进微管蛋白聚合。先前的工作表明，GABARAP 家族成员（GABARAP、LC3、GATE-16 和 Atg8）不仅参与蛋白质或囊泡的运输，而且还涉及各种机制，如自噬、细胞死亡、细胞增殖和肿瘤进展。因此，我们询问 GABARAPL1 是否也可能在自噬中发挥作用。首先，我们表明 GABARAPL1 在甘氨酸 116 处被切割，该残基在家族的其他成员中保守。我们还证明 GABARAPL1 与磷脂相连，被 Atg4B 去脂酰化，与细胞内膜相关，并在溶酶体活性抑制后积累在细胞内囊泡中。最后，我们表明 GABARAPL1 与 LC3 或 Lysotracker green 在细胞内囊泡中部分共定位。总之，我们的结果表明 GABARAPL1 与自噬囊泡相关。
