Moonlighting functions of the NRZ (mammalian Dsl1) complex

Abstract

The yeast Dsl1 complex, which comprises Dsl1, Tip20, and Sec39/Dsl3, has been shown to participate, as a vesicle-tethering complex, in retrograde trafficking from the Golgi apparatus to the endoplasmic reticulum. Its metazoan counterpart NRZ complex, which comprises NAG, RINT1, and ZW10, is also involved in Golgi-to-ER retrograde transport, but each component of the complex has diverse cellular functions including endosome-to-Golgi transport, cytokinesis, cell cycle checkpoint, autophagy, and mRNA decay. In this review, we summarize the current knowledge of the metazoan NRZ complex and discuss the "moonlighting" functions and intercorrelation of their subunits.

Keywords: CATCHR tether complex; NAG; RINT1; ZW10; autophagy; cell cycle; endoplasmic reticulum; mRNA decay.

Figure 1

Subunit compositions of the Dsl1 (A), NRZ (B), and RZZ (C) complexes. ZWINT is not included in the RZZ complex, but shown here because it may have a role corresponding to Tip20/RINT1 in the Dsl1/NRZ complexes. The ZW10-binding site on ROD has not been mapped. N and C indicate the N- and C-terminal regions, respectively.

Figure 2

Interactions between tethers and SNAREs. (A) On yeast ER membranes, Tip20 and Sec39 bind to the N-terminal regions (N) of Sec20 and Use1/Slt1, respectively. The region of Dsl1 shown in blue represents an acidic region that interacts with COPI components. (B) On the mammalian ER, RINT1 and NAG bind to the N-terminal regions of BNIP1 and Use1/p31, respectively. (C) On the mammalian TGN, SNAREs binds the COG complex directly or indirectly through RINT1. The COG complex model (Oka et al., ; Ungar et al., 2005) has been slightly modified. N and C indicate the N- and C-terminal regions, respectively.

Figure 3

Correlation diagram of NRZ complex subunits. ZW10 is the center for the interactions. Through its N-terminal, putative coiled-coil region, it interacts with RINT1 for membrane trafficking (Hirose et al., ; Inoue et al., 2008), dynamitin for recruiting the dynein-dynactin complex (Starr et al., ; Inoue et al., 2008), ZWINT for the association with kinetochores (Wang et al., ; Kops et al., 2005). The C-terminal region of ZW10 likely interacts with NAG and ROD (Kraynack et al., ; Aoki et al., ; Civril et al., 2010). The interaction of Zwilch with ZW10 is not tight in the absence of ROD (Civril et al., 2010). On the other hand, RINT1 interacts with COG1 through its N-terminal, putative coiled-coil region (Arasaki et al., 2013). This interaction mode may be a common for the interactions of CATCHR family members. The N-terminal region is also responsible for the interaction with UVRAG, but in this case, RINT1 keeps the binding to ZW10 (He et al., 2013). The RINT1 interacts with RAD50 and RBL2/p130. UVRAG interacts with RINT1 under basal conditions and, upon starvation, dissociates from RINT1 and interacts with Beclin1. Of note is that Beclin1 during mitosis interacts with ZWINT, a ZW10 partner.