Figure 6

Proposed model of Nef-mediated enhancement of nanotube formation via the exocyst complex. Based on proteomics data and protein interaction networks shown in Table 1 and Figure 4, a model of Nef-mediated enhancement of nanotube formation and microvesicle release is shown (described in the text). Briefly, Nef i) traffics to recycling endosomes via enhanced endocytosis, ii) upregulates exocyst complex assembly via Pak2-stimulated Aurora kinase activation (AURKA) [71] and phosphorylation and relocalization of RalA [73], and iii) budding of Nef-bearing vesicles from recycling endosomes [75, 76] and enhances iv) Nef secretion in microvesicles (see “tether and burst”) [25] and v) nanotube formation via exocyst complex function, thereby increasing intercellular transfer of Nef. Protein complexes denoted in boxes act at the indicated steps. The exocyst complex is abbreviated as “E8” and depicted as green octagons.