Multiple endocytic processes operate in cells in tandem to uptake multiple cargoes involved in diverse cellular functions, including cell adhesion and migration. The best-studied clathrin-mediated endocytosis (CME) involves the formation of a well-defined cytoplasmic clathrin coat to facilitate cargo uptake. According to the glycolipid–lectin (GL–Lect) hypothesis, galectin-3 (Gal3) binds to glycosylated membrane receptors and glycosphingolipids (GSLs) to drive membrane bending and tubular membrane invaginations that undergo scission to form a morphologically distinct class of uptake structures, termed clathrin-independent carriers (CLICs). Which components from cytoskeletal machinery are involved in the scission of CLICs remains to be explored. In this study, we propose that dynein is recruited onto Gal3-induced tubular endocytic pits and provides the pulling force for friction-driven scission. The uptake of Gal3 and its cargoes (CD98/CD147) is significantly dependent on dynein activity, whereas only transferrin (CME marker) is slightly affected upon dynein inhibition. Our study reveals that Gal3 and Gal3-dependent (CD98 and CD147) clathrin-independent cargoes require dynein for the clathrin-independent endocytosis.

多个内吞过程在细胞中串联运行，以摄取参与不同细胞功能（包括细胞粘附和迁移）的多种货物。研究最充分的网格蛋白介导的内吞作用 (CME) 涉及形成明确的细胞质网格蛋白外壳，以促进货物的摄取。根据糖脂-凝集素 (GL-Lect) 假说，半乳糖凝集素-3 (Gal3) 与糖基化膜受体和鞘糖脂 (GSL) 结合，驱动膜弯曲和管状膜内陷，从而发生分裂，形成形态上独特的一类摄取结构，称为网格蛋白独立携带者（CLIC）。细胞骨架机制的哪些成分参与了 CLIC 的分裂仍有待探索。在这项研究中，我们提出动力蛋白被招募到 Gal3 诱导的管状内吞凹坑上，并为摩擦驱动的断裂提供拉力。Gal3 及其货物 (CD98/CD147) 的摄取显着依赖于动力蛋白活性，而只有转铁蛋白（CME 标记）受到动力蛋白抑制的轻微影响。我们的研究表明，Gal3 和 Gal3 依赖性（CD98 和 CD147）网格蛋白独立货物需要动力蛋白来进行网格蛋白独立内吞作用。