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.

Alterations of autophagy in the peripheral neuropathy Charcot-Marie-Tooth type 2B

“…35 , 42 , 46–48 Indeed, by first using a HeLa model cell system, we demonstrate that, different from the wild-type protein, these mutants fail to increase the number of autophagosomes both in basal conditions and after stimulation, behaving similarly to the dominant negative and functionally impaired RAB7 T22N mutant. Still, while model cell lines are widely used as easily manageable tools to understand molecular mechanisms involved in a wide variety of cellular phenomena, they do not necessarily fully recapitulate the biological conditions of affected cells in vivo.…”

“…12 , 41 , 42 However, to verify that indeed CMT2B mutations in this gene do not affect also early phases of autophagosomal biogenesis, we evaluated the expression of the ATG12–ATG5 complex upon prolonged serum starvation. 38 , 39 , 43 Interestingly, ATG12–ATG5 levels similarly increased in normal and CMT2B fibroblasts, indicating that autophagosomal biogenesis was not affected by the RAB7 V162M mutation (Fig.…”

Control of RAB 7 activity and localization through the retromer‐TBC1D5 complex enables RAB 7‐dependent mitophagy

“…Although retromer is known to be a RAB7 effector that depends on this small GTPase for its localization to the endosomal membrane (Seaman et al , ; Harrison et al , ), the precise relationship or any potential cross‐regulation between retromer and RAB7 has not been investigated in depth. RAB7 is known to be a key organizer/regulator of the late endosomal/lysosomal network that associates with various effectors to orchestrate diverse functions such as lysosomal biogenesis, late endosome–lysosome fusion, autophagosome maturation, and cargo transport within the late endocytic network (Guerra & Bucci, ). The activation of RAB7 through the MON1/CCZ1 complex is needed for endosome maturation (Kinchen & Ravichandran, ; Nordmann et al , ; Poteryaev et al , ; Gerondopoulos et al , ), whereas several RAB7‐specific GAPs have been implicated in autophagy, mitophagy, and the degradative pathway (Frasa et al , ; Carroll et al , ; Yamano et al , ).…”

Missing-in-metastasis protein downregulates CXCR4 by promoting ubiquitylation and interaction with small Rab GTPases

“…The intracellular process of CXCR4 internalization is initiated upon phosphorylation at its C-terminus, followed by ubiquitylation and subsequent sorting into early endosomes, which are then processed into late endosomes or multivesicular bodies (MVBs) and further fused with lysosomes, in which the receptor and its bound ligand are degraded. The maturation of endosomes involves a cascade of cellular processes that is controlled by Rab small GTPases (Guerra and Bucci, 2016;Mizuno-Yamasaki et al, 2012). In particular, the transition from Rab5 to Rab7 enrichment on membranes signals the maturation of MVBs, which contain characteristic intraluminal vesicles.…”