Nag Zw10 Nrz Complex

However, as the ER is a major source of autophagosome formation reviewed by Lamb et al., 2013, RINT1 and other NRZ complex subunits may have more active roles in autophagy. Schmitt 2010 has proposed that the ancestor of animals and fungi probably expressed both sets of ZW10-interacting proteins NAG- RINT1 and ROD-Zwilch. Rod and Zwilch

ZW10 binding to ROD and NAG is mutually exclusive. The resulting ZW10 complexes RZZ and NRZ respectively contain ZWILCH and RINT1 as additional subunits. The X-ray structure of ZWILCH, the first for an RZZ subunit, reveals a novel fold distinct from RINT1's. The evolutionarily conserved NRZ likely acts as a tethering complex for retrograde

The NRZ complex NAG, RINT1, and ZW10 plays a key role in mediating ER-localized SNAREs Syntaxin18, Use1, and BNIP1 to form MCSs with Rab18 on LDs adapted from Wu et al., 2018. Created by BioRender httpsbiorender.com. A key regulator of lipid droplets LDs is the small GTPase Rab18 protein.

In a guanosine 5-triphosphate-dependent manner, Rab18 is recruited to the LD surface and specifically to the ER-associated NAG-RINT1-ZW10 NRZ complex and SNARE soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins Syntaxin18, Use1, and BNIP1 . Consistent with the ER-LD linker activity, depletion of Rab18, NRZ

In this process, LD's Rab18 was found to physically associate with an ER-associated complex comprising the NRZ complex with its subunits NAG, RINT1, and ZW10, associated with SNARE Syntaxin 18

LD-associated Rab18 bound specifically to the ER-associated NAG-RINT1-ZW10 NRZ tethering complex and their associated SNAREs Syntaxin18, Use1, BNIP1, resulting in the recruitment of ER to LD and the formation of direct ER-LD contact. Cells with defects in the NRZSNARE complex function showed reduced LD growth and lipid storage.

The two complexes in question, called Rod-Zw10-Zwilch RZZ and Nag-Rint1-Zw10 NRZ, respectively, were already known to share the Zw10 subunit, but as the new report describes, the similarity extends to the homolog of Tip20p, and the protein Nag. Nag was independently identified in complex with Zw10 by two different groups by Aoki et

The ZW10 protein is shown to be part of two structurally related complexes, the RZZ and the NRZ ROD and NAG, subunits of the RZZ and NRZ, respectively, consist of a propeller and an solenoid This organization is typical of clathrin, COP-I, and nucleoporins, suggesting the RZZ evolved from them A crystal structure of ZWILCH, an RZZ subunit, is reported and shown to have a novel fold