Macropinocytosis is the non-selective uptake of large quantity of solute and membrane into cells. This actin-dependent process initiates from plasma membrane ruffles giving rise to macropinosomes. Macropinocytosis is utilised by antigen presenting cells for antigen sampling, is relevant to cell migration and metastasis and is also a portal of cell entry exploited by a range of pathogens.
Sorting nexins (SNXs) have been implicated in cargo trafficking in the endocytic pathway. In particular, SNX5 has a PX domain which exhibits dual phosphoinositide specificity for PtdIns(3)P and PtdIns(3,4)P2.We have previously reported that the level of SNX5 influences macropinocytosis in HEK293 cells (Lim et al., 2008).
We have analyzed the role SNX5 and its binding partner, SNX1, in macropinocytosis of mouse primary macrophages. We show that endogenous SNX1 and SNX5 are localised to newly-formed macropinosomes and moreover, demonstrate that SNX5 plays an essential role in macropinosome biogenesis. Depletion of SNX5 in bone marrow-derived macrophages decreased the number and size of macropinosomes. Depletion of SNX5 also resulted in reduction in uptake and processing of ovalbumin in macrophages. By contrast, absence of SNX1 had no effect on macropinosome biogenesis using macrophages from SNX1 knockout mice. Therefore, SNX5 can function independently of SNX1 and is a modulator of macropinocytosis; influencing uptake and processing of soluble antigen in primary mouse macrophages.
Elevated expression of SNX5 has also been identified in papillary thyroid carcinoma, an endocrine malignant tumour (Ara et al., 2012). We have analysed the role of SNX5 in cell proliferation and shown that depletion of SNX5 in NIH3T3 fibroblasts results in an increase in size of the cells and a reduced cell proliferation. These data suggests that SNX5, in addition to regulating macropinocytosis, may have a role in regulating cell proliferation.