TRAPPC9 Mediates the Interaction between p150Glued and COPII Vesicles at the Target Membrane

Abstract

BackgroundThe transport of endoplasmic reticulum (ER)-derived COPII vesicles toward the ER-Golgi intermediate compartment (ERGIC) requires cytoplasmic dynein and is dependent on microtubules. p150Glued, a subunit of dynactin, has been implicated in the transport of COPII vesicles via its interaction with COPII coat components Sec23 and Sec24. However, whether and how COPII vesicle tether, TRAPP (Transport protein particle), plays a role in the interaction between COPII vesicles and microtubules is currently unknown.Principle FindingsWe address the functional relationship between COPII tether TRAPP and dynactin. Overexpressed TRAPP subunits interfered with microtubule architecture by competing p150Glued away from the MTOC. TRAPP subunit TRAPPC9 bound directly to p150Glued via the same carboxyl terminal domain of p150Glued that binds Sec23 and Sec24. TRAPPC9 also inhibited the interaction between p150Glued and Sec23/Sec24 both in vitro and in vivo, suggesting that TRAPPC9 serves to uncouple p150Glued from the COPII coat, and to relay the vesicle-dynactin interaction at the target membrane.ConclusionsThese findings provide a new perspective on the function of TRAPP as an adaptor between the ERGIC membrane and dynactin. By preserving the connection between dynactin and the tethered and/or fused vesicles, TRAPP allows nascent ERGIC to continue the movement along the microtubules as they mature into the cis-Golgi.

A microtubule-independent role of p150glued in secretory cargo concentration at endoplasmic reticulum exit sites

“…A possible protein contributing to this process is TRAPPC9, a component of the transport protein particle (TRAPP) tether complex. This protein binds to the same p150 glued domain as SEC23 and inhibits the interaction of SEC23-SEC24 with p150 glued disrupting the colocalization of ERES and p150 glued (Zong et al, 2012). Indeed, the competition of SEC23 and TRAPPC9 for the same domain of p150 glued might be key for the role of p150 glued at different stages of ER-to-Golgi transport.…”

Elevated NIBP/TRAPPC9 mediates tumorigenesis of cancer cells through NFκB signaling

“…NIBP was recently renamed as trafficking protein particle complex 9 (TRAPPC9) because it is identical to yeast Trs120 protein, an essential and unique subunit for the TRAPP II complex that regulates the trans -Golgi exit process [19-22]. The trans -Golgi network is essential for cancer development and may represent a novel target for anti-cancer therapy [23].…”

Retrograde Traffic from the Golgi to the Endoplasmic Reticulum

“…However, some of the destabilized coat components have to stay on the vesicle until it has reached the Golgi apparatus because coat components participate in the recognition and the tethering process (Barlowe 1997;Cai et al 2007;Lord et al 2011;Zong et al 2012). Subsequently, SNARE proteins on the vesicles (v-SNAREs) zipper up with cognate SNAREs on the Golgi (target SNAREs, tSNAREs) to drive membrane fusion (Hay et al 1998;Cao and Barlowe 2000;Parlati et al 2002).…”