Despite having identified multiple membrane trafficking regulator proteins implicated in the removal of MHC-I from the cell surface, it remains unknown what cellular compartments are used by Nef during this process precluding our understanding of the pathway subverted by HIV-1 to evade immune surveillance.
In summary, it seems that collectrin is necessary for the maintenance of primary cilium to supply the primary cilia-specific integral membrane proteins, including polycystin-2, and it is involved in multiple membrane trafficking processes; vesicle transport, docking to base of primary cilia, ER-Golgi trafficking, and intraciliary recycling.
The vps-15 gene was identified in budding yeast due to its requirement for vacuolar (lysosomal) protein sorting and acts in multiple membrane trafficking processes (Backer 2008).
For instance, the endoplasmic reticulum (ER) and the plasma membrane (PM) cannot fuse directly, but they are functionally connected through multiple membrane traffic steps, a time-consuming process.
These findings suggest that VAMP7 may associate with a variety of other SNARE partners to function in multiple membrane traffic steps which may in part be cell type-specific [ 42].
Indeed, Nef interacts with multiple proteins implicated in membrane trafficking in order to downregulate cell surface levels of major histocompatibility complex class I (MHC-I), resulting in a decreased ability of infected CD4+ T-cells to be detected and killed by CD8+ cytotoxic T lymphocytes (CTLs 5.
Among the substrates for palmitoylation are Vac8, SNAREs, and Ras2, indicating important regulatory functions for this FA modification of proteins in multiple pathways involved in membrane trafficking and signaling.
The huntingtin protein is ubiquitously expressed in the brain and has multiple roles in cellular membrane trafficking, including anterograde axonal transport of neurotrophic factors [such as brain-derived neurotrophic factor (BDNF)] for release from cortical neurons.
Membrane microdomains have been implicated as being important for multiple biological processes, including membrane trafficking, cell signalling and exocytosis (reviewed by Simons and Toomre, 2000; Salaün et al., 2004; Gupta and DeFranco, 2007; Jury et al., 2007; Simons and Gerl, 2010).
Huntingtin has multiple roles in cellular membrane trafficking and associates with microtubule-based kinesin and dynein motor proteins, but is also linked via its interacting protein optineurin with the actin-associated motor myosin VI (Hattula and Peränen, 2000; Sahlender et al., 2005; Bond et al., 2011).
The ability of the PIs to serve the multiple and dynamic functions in membrane trafficking mentioned above is due to the tight spatial and temporal control of their generation/consumption, that is, of the PIKs and PI phosphatases.
