[Effectors of GTPase Rab5 in endocytosis and signal transduction].

Small GTPase Rab5 is a multifunctional protein, which regulates early steps of endocytosis, due to its interactions with numerous effectors such as: Rabaptin-5/Rabex-5, EEA1, phosphatidylinositol 3-kinases hVPS34-p150 and p110beta-p85alpha, phosphatidylinositol 4- and 5-phosphatases, Rabenosyn-5/hVPS45, Rabankyrin-5, Huntingtin-HAP40, APPL1 and APPL2. These proteins specifically bind to the active form of Rab5, thus regulating the processes of docking and fusion of endosomal membranes, motility of endosomes and intracellular signal transduction. The characterization of molecular mechanisms underlying interactions of Rab5 effectors with membranes of early endosomes demonstrated that phosphatidylinositol 3-phosphate (PI(3)P) is a key component in this process. This further led to a concept of Rab domains as functional units of endosomal membranes, contributing to the biochemical and functional identity of these organelles. In turn, studies of APPL1 and APPL2 proteins illustrated a role of Rab5 in coordinated regulation of endocytosis and signal transduction.