Figure 6: A possible model for a PX-RICS-dependent cargo-motor interconnection.

(a) The multiple domains mediating protein–protein and protein–phospholipid interactions of PX-RICS enables PX-RICS to play a central role as a scaffold in assembling the constituents of the trafficking complex. Cargo recognition is conducted by GABARAP through its binding to the cytoplasmic region of the γ2 subunit³¹. GABARAP also serves as a binding cue for PX-RICS. Crystal structure analysis has revealed that GABARAP can self-associate in a head-to-tail manner⁶⁶, and this oligomerization activity may underlie its multitasking ability. Phosphorylation of PX-RICS by CaMKII induces the sequential assembly of 14-3-3ζ/θ and dynein/dynactin²³. By interconnecting the transport-competent γ2-containing GABA_AR complex with the dynein/dynactin motor complex, the PX-RICS/GABARAP/14-3-3 adaptor complex facilitates GABA_AR transport from the somatodendritic secretory compartments to the neuronal surface. (b) A previously proposed trafficking model for the N-cadherin/β-catenin (β-cat) complex^22,23. Cargo recognition is accomplished by PX-RICS through its binding ability to β-catenin. GABARAP provide a binding cue to PX-RICS to anchor it on the endoplasmic reticulum membrane. See also our previous papers for further details^22,23. Recently, it has become apparent that an increasing number of plasma membrane-bound receptors depend on GABARAP for their cell surface expression^{22,23,32,67,68,69,70}. Thus, the PX-RICS-dependent adaptor system may be implicated in the delivery of a wide variety of cell surface proteins.