RUFY, Rab and Rap Family Proteins Involved in a Regulation of Cell Polarity and Membrane Trafficking

Abstract

Cell survival, homeostasis and cell polarity rely on the control of membrane trafficking pathways. The RUN domain (comprised of the RPIP8, UNC-14, and NESCA proteins) has been suggested to be implicated in small GTPase-mediated membrane trafficking and cell polarity. Accumulating evidence supports the hypothesis that the RUN domain-containing proteins might be responsible for an interaction with a filamentous network linked to actin cytoskeleton and/or microtubules. In addition, several downstream molecules of PI3K are involved in regulation of the membrane trafficking by interacting with vesicle-associated RUN proteins such as RUFY family proteins. In this review, we summarize the background of RUN domain research with an emphasis on the interaction between RUN domain proteins including RUFY proteins (designated as RUN and FYVE domain-containing proteins) and several small GTPases with respect to the regulation of cell polarity and membrane trafficking on filamentous network.

Rab31 promoted hepatocellular carcinoma (HCC) progression via inhibition of cell apoptosis induced by PI3K/AKT/Bcl-2/BAX pathway

“…It is critical for these multidirectional transports to be adequately modulated, and abnormity at any point of membrane transport network could result in diseases [4]. Rab GTPases, which belong to the Ras superfamily of small GTPbinding proteins, are important mediators for membrane transport of both lipid and protein in human cells [5].…”

Retracted Article: Down-regulation of Rab10 inhibits hypoxia-induced invasion and EMT in thyroid cancer cells by targeting HIF-1α through the PI3K/Akt pathway

“…11 These processes, in turn, mediate the normal membrane polarity. [12][13][14] Besides, these Rab GTPases can be activated by distinct types of Rab GEFs and down-regulated by Rab GAPs. 15 Rab10, a member of the Rab family, is an important participant in formation of endoplasmic reticulum, secretion of basement membrane and translocation of glucose transporter type 4.…”

Rufy3 is an adapter protein for small GTPases that activates a Rac guanine nucleotide exchange factor to control neuronal polarity

“…These proteins share several common biochemical properties; for example, their activated (GTP-bound) form is selectively bound to specific adapter proteins for signal trans-duction (1). A group of such adapter proteins was recently shown to contain a RUN domain which is involved in binding small G proteins (2) of which one, RUN and FYVE domaincontaining 3 (Rufy3; 2 also known as Singar1/Rap2-interacting protein X), lacks an FYVE domain, which interacts with phosphatidylinositol 4,5-bisphosphate, and therefore cannot directly associate with the cell membrane (2). The analysis of Rufy3 using X-ray crystallography has shown that Rap2, a Ras family member, is tightly and stably bound to Rufy3 in a GTPand RUN domain-dependent manner (3).…”