Multiple Roles of the Small GTPase Rab7

Abstract

Rab7 is a small GTPase that belongs to the Rab family and controls transport to late endocytic compartments such as late endosomes and lysosomes. The mechanism of action of Rab7 in the late endocytic pathway has been extensively studied. Rab7 is fundamental for lysosomal biogenesis, positioning and functions, and for trafficking and degradation of several signaling receptors, thus also having implications on signal transduction. Several Rab7 interacting proteins have being identified leading to the discovery of a number of different important functions, beside its established role in endocytosis. Furthermore, Rab7 has specific functions in neurons. This review highlights and discusses the role and the importance of Rab7 on different cellular pathways and processes.

Keywords: Rab7; apoptosis; autophagy; endocytosis; intermediate filaments; lipophagy; lysosome; membrane traffic; mitophagy; vesicular transport.

Figure 1

Multiple roles of Rab7. Rab7 has different roles in several crucial cellular functions.

Figure 2

Rab7 in the late endocytic pathway and in retromer regulation: (A) sequential and dynamic cooperation between Rab5 and Rab7 to determine the Rab5 to Rab7 switch; (B) RILP interaction with HOPs complex for late endosome-lysosome fusion and Rab7–RILP interaction to regulate assembly and function of the V-ATPase for acidification; (C) movement of late endosomes on microtubules is determined by interaction of Rab7 with RILP and FYCO1 for minus-end and plus-end direction, respectively; and (D) retrograde transport of transmembrane cargo from endosomes to the TGN is regulated by interaction between Rab7 and subunits of the retromer complex.

Figure 3

Rab7 in macroautophagy, mitophagy and lipophagy: (A) importance of Rab7 in docking, fusion and autophagosome clustering during macroautophagy; (B) Rab7 promotes the growth of the isolation membrane through microtubule associated trafficking but subsequently Rab7 inactivation is necessary for correct shaping of the autophagosomal membrane around mitochondria; and (C) increased Rab7 activation allows autophagy of LDs, a process named lipophagy. The autophagosome fuses with endocytic Rab7-positive degradative compartments to eventually form an autolysosome for lipid degradation.

Figure 4

Multiple roles of Rab7 in Neurons. Rab7 has a crucial role in different neuronal processes.