人类细胞中有超过60种RAB蛋白,它们参与了内溶酶体系统中蛋白质的运输。这些小的GTPases通过定位于不同内吞室的细胞膜,并与诸如分选适配器、栓系因子、激酶、磷酸酶和管状囊泡货物等效应物相互作用,促进了运输特异性(Stenmark et al, 2009;wanderingness and Zerial, 2014)。RAB的定位取决于很多因素,包括c端前酰化、上游高变区序列以及结合的核苷酸(Chavrier et al ., 1991;乌尔里希等人,1993;Soldati等人,1994;范斯沃斯等人,1994;Seabra, 1996;Wu et al, 2010;《Stenmark》,2009; Wandinger-Ness and Zerial, 2014). In the active, GTP-bound form, prenylated RAB proteins are membrane associated, while in the inactive GDP-bound form, RABs are extracted from the target membrane and exist in a soluble form in complex with GDP dissociation inhibitors (GDIs) (Ullrich et al, 1993; Soldati et al, 1994; Gavriljuk et al, 2103). Conversion between the inactive and active form relies on the activities of RAB guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) (Yoshimura et al, 2010; Wu et al, 2011; Pan et al, 2006; Frasa et al, 2012; reviewed in Stenmark, 2009; Wandinger-Ness and Zerial, 2014).
新合成的RABs由RAB护航蛋白CHM(也称为REP1)或CHML (REP2)结合(Alexandrov et al, 1994;Shen and Seabra, 1996)。CHM/REP蛋白是三聚RAB香叶酰香叶酰转移酶(GGTaseII)的底物结合成分,以及RABGGTA和RABGGTB两个催化亚基(Gutkowska和Swiezewska, 2012;Palsuledesai and Distefano, 2015)。REP蛋白将未修饰的与gdp结合的RAB招募到GGTase上,在一个或两个c端半胱氨酸残基上进行香叶酰香叶酰化(Alexandrov et al ., 1994;Seabra等人1996年;Shen and Seabra, 1996;Baron and Seabra, 2008)。在香叶酰香叶酰化后,CHM/REP蛋白仍然与香叶酰香叶酰化的RAB形成复合物,并将其护送至目标膜,其活性受到gap、gef、GDIs和膜结合GDI置换因子(gfs)的调控(Sivars et al ., 2003;《Stenmark》,2009; Wandinger-Ness and Zerial, 2014).