The Phox Homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation

Recent studies have shown that phox homology (PX) domains act as phosphoinositide-binding motifs. The majority of PX domains studied show binding to phosphatidylinositol 3-monophosphate (Ptdlns(3)P), an association that allows the host protein to localize to membranes of the endocytic pathway. One issue, however, is whether PX domains may have alternative phosphoinositide binding specificities that could target their host protein to distinct subcellular compartments or allow their allosteric regulation by phosphoinositides other than PtdIns(3)P. It has been reported that the PX domain of sorting nexin 1 (SNX1) specifically binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3) (Zhong, Q., Lazar, C. S., Tronchere, H., Sato, T., Meerloo, T., Yeo, M., Songyang, Z., Emr, S. D., and Gill, G. N. (2002) Proc. Natl. Acad. Sci. U. S. A. 99,6767-6772). In the present study, we have shown that whereas SNX1 binds PtdIns(3,4,5)P-3 in protein:lipid overlay assays, in liposomes-based assays, binding is observed to PtdIns(3)P and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P-2) but not to PtdIns(3,4,5)P-3. To address the significance of PtdIns(3,4,5)P-3 binding, we examined the subcellular localization of SNX1 under conditions in which plasma membrane PtdIns(3,4,5)P-3 levels were significantly elevated. Under these conditions, we failed to observe association of SNX1 with this membrane. However, consistent with the binding to PtdIns(3)P and PtdIns(3,5)P-2 being of more physiological significance was the observation that the association of SNX1 with an early endosomal compartment was dependent on a 3-phosphoinositide-binding PX domain and the presence of PtdIns(3)P on this compartment. Finally, we somal association of SNX1 is important for its ability to regulate the targeting of internalized epidermal growth factor receptor for lysosomal degradation.

Monarchs in Australia: On the winds of a storm?

The monarch butterfly, Danaus plexippus, is one of Australia's best-known exotic butterflies, being first recorded here in the spring/summer of 1870/1871. However, the source of the original population is unknown. Using historical records we suggest that the most likely source of the founder population was from Vanuatu and/or New Caledonia. Many almost simultaneous 'first records' for the butterfly in Australia suggest that a large, well-distributed population was present when first noticed. While such a population may have developed from a limited number of individuals flying across the Coral Sea, the well documented, very dramatic appearance of large monarch populations in Australia does not appear to fit this model. Rather, we hypothesise that large numbers of monarchs were carried to Australia on cyclonic winds: no fewer that 3 cyclones hit the Queensland coast in early 1870. If one or more of these cyclones tracked from the Vanuatu/New Caledonia chain, then they may have transported monarchs. Once established on the central/northern Queensland coast, natural migration would account for the appearance of butterflies further south.

Walking towards health in a university community: Preliminary analyses of baseline data

Research has shown that accumulating 10 000 steps/day provides a range of significant clinical health benefits. However, opportunities for daily walking are constrained by a number of barriers, including employment in sedentary occupations.