OCRL1 engages with the F-BAR protein pacsin 2 to promote biogenesis of membrane-trafficking intermediates.

Mutation of the inositol 5-phosphatase OCRL1 causes Lowe syndrome and Dent-2 disease. Loss of OCRL1 function perturbs several cellular processes, including membrane traffic, but the underlying mechanisms remain poorly defined. Here we show that OCRL1 is part of the membrane-trafficking machinery operating at the trans-Golgi network (TGN)/endosome interface.

Inositol lipid phosphatases in membrane trafficking and human disease.

The specific interaction of phosphoinositides with proteins is critical for a plethora of cellular processes, including cytoskeleton remodelling, mitogenic signalling, ion channel regulation and membrane traffic. The spatiotemporal restriction of different phosphoinositide species helps to define compartments within the cell, and this is particularly important for membrane trafficking within both the secretory and endocytic pathways. Phosphoinositide homoeostasis is tightly regulated by a large number of inositol kinases and phosphatases, which respectively phosphorylate and dephosphorylate distinct phosphoinositide species.

The cytosolic N-terminus of CD317/tetherin is a membrane microdomain exclusion motif.

The integral membrane protein CD317/tetherin has been associated with a plethora of biological processes, including restriction of enveloped virus release, regulation of B cell growth, and organisation of membrane microdomains. CD317 possesses both a conventional transmembrane (TM) domain and a glycophosphatidylinositol (GPI) anchor. We confirm that the GPI anchor is essential for CD317 to associate with membrane microdomains, and that the TM domain of CD44 is unable to rescue proper microdomain association of a ΔGPI-CD317 construct.

Expression of HIV-1 Vpu leads to loss of the viral restriction factor CD317/Tetherin from lipid rafts and its enhanced lysosomal degradation.

CD317/tetherin (aka BST2 or HM1.24 antigen) is an interferon inducible membrane protein present in regions of the lipid bilayer enriched in sphingolipids and cholesterol (often termed lipid rafts). It has been implicated in an eclectic mix of cellular processes including, most notably, the retention of fully formed viral particles at the surface of cells infected with HIV and other enveloped viruses.

CD317/tetherin is an organiser of membrane microdomains.

The integral membrane protein tetherin has been associated with an eclectic mix of cellular processes, including restricting the release of a range of enveloped viruses from infected cells. The unusual topology of tetherin (it possesses both a conventional transmembrane domain and a glycosylphosphatidylinositol anchor), its localisation to membrane microdomains (lipid rafts) and the fact that its cytosolic domain can be linked (indirectly) to the actin cytoskeleton, led us to speculate that tetherin might form a 'tethered picket fence' and thereby play a role in the organisation of lipid rafts. We now show that knocking down expression of tetherin leads to changes in the distribution of lipid raft-localised proteins and changes in the organisation of lipids in the plasma membrane.