RAB6:GTP and BICD homodimers bind COPI-independent Golgi-to-ER retrograde cargo

COPI-independent retrograde traffic from the Golgi to the ER depends on RAB6 and involves formation of membrane tubules instead of classical transport vesicles. COPI-dependent and COPI-independent retrograde transport appear to have distinct cargo, as anti-COPI antibodies inhibit the traffic of KDEL-containing receptors, but not that of Shiga or Shiga-like toxins, or of Golgi-resident glycosylation enzymes (White et al, 1999; Girod et al, 1999). It is not yet clear how membrane tubules formation is initiated, however cargo type and concentration, as well as lipid composition may contribute (Martinez et al, 1997; Simpson et al, 2006; de Figueiredo et al, 1998; de Figueiredo et al, 1999; reviewed in Heffernan and Simpson 2014). The presence of sn2-lysophospholipids in the Golgi membrane generates curved membranes that are thought to favour tubule formation. Lysophospholipids are generated by the activity of phopholipase A2 enzymes that hydrolyze the fatty acid at the sn-2 position; this activity is counteracted by the activity of lysophospholipid acyltransferases (LPATs). The balance of these two activities at the Golgi membrane is thought to play a role in determining whether COPI-dependent or -independent transport is favoured (de Figueiredo et al, 1998; de Figueiredo et al, 1999; Schmidt et al, 2009; reviewed in Heffernan and Simpson, 2014). Recent studies have also implicated the coiled coil homodimer Bicaudal-D (BICD) proteins in COPI-independent retrograde traffic. BICD proteins bind RAB6:GTP with their C-terminal ends and the dynein:dynactin motor complex with their N-terminal ends and in this way are thought to facilitate the recruitment of motor proteins to the RAB6 retrograde pathway (Hoogenraad et al, 2001; Matanis et al, 2002; Young et al, 2005; Januschke et al, 2007).

高尔基体向内质网的COPI非依赖性逆行运输依赖于RAB6，并涉及膜管的形成而非经典的运输囊泡。COPI依赖性和COPI非依赖性逆行运输似乎具有不同的货物，因为抗COPI抗体可抑制包含KDEL的受体的运输，但不能抑制志贺氏菌或志贺氏菌样毒素，或高尔基体驻留的糖基化酶的运输（White等人，1999；Girod等人，1999）。然而，关于膜管形成的起始机制尚不明确，但货物类型和浓度，以及脂质组成可能起到一定的作用（Martinez等人，1997；Simpson等人，2006；de Figueiredo等人，1998；de Figueiredo等人，1999；参见Heffernan和Simpson 2014年的综述）。高尔基体膜中sn2-溶血磷脂的存在生成了有利于管状形成弯曲的膜。溶血磷脂由磷脂酶A2酶的活性产生，这些酶在sn-2位置水解脂肪酸；这一活性被溶血磷脂酰基转移酶（LPATs）的活性所抵消。据认为，这两种活性在高尔基体膜中的平衡在决定是优先选择COPI依赖性还是非依赖性运输中发挥作用（de Figueiredo等人，1998；de Figueiredo等人，1999；Schmidt等人，2009；参见Heffernan和Simpson，2014年的综述）。最近的研究还暗示了卷曲同源二聚体Bicaudal-D（BICD）蛋白在COPI非依赖性逆行运输中的作用。BICD蛋白以其C端与RAB6:GTP结合，以其N端与dynein:dynactin马达复合物结合，从而被认为有助于将马达蛋白招募到RAB6逆行途径中（Hoogenraad等人，2001；Matanis等人，2002；Young等人，2005；Januschke等人，2007）。