Macropinocytosis is the non-selective uptake of large quantity of solute and membrane into cells. This actin-dependent endocytic pathway initiates from plasma membrane ruffles giving rise to macropinosomes. Macropinocytosis is utilised by antigen presenting cells for antigen sampling and, unfortunately, exploited by a range of pathogens as portal of cell entry. In addition, the macropinocytic pathway is utilised by Ras-transformed cells to support their metabolic needs (Commisso et al., 2013) and, being an actin-dependent process, is relevant to cell migration/metastasis.
Sorting nexins (SNXs), a family of proteins classified by the presence of a phox-homology (PX) domain, have been implicated in cargo and membrane trafficking in the endocytic pathway. We have previously reported that the level of SNX5 influences macropinocytosis in HEK293 cells (Lim et al. 2008) and cultured mouse primary macrophages (Lim et al., 2012). Indeed, depletion of SNX5 using RNA interference decreased the number and size of macropinosomes as well as reduced uptake and processing of ovalbumin in cultures primary macrophages. Thus, demonstrating a role for SNX5 in macropinosome biogenesis and uptake/ processing of soluble antigen in mouse macrophages.
We have recently established a SNX5 “Knock-out First” mouse that allows us to investigate the physiological functions of SNX5 in vivo. Using cells from the SNX5 “Knock-out First” mouse, we are also able to study the role of SNX5 in other forms of endocytosis such as the classical clathrin-dependent and phagocytic pathway.