Of Caveosomes

HIGHLIGHTS

MEMBRANE TRANSPORT Of caveosomes ... We knew that simian virus 40 (SV40) is unusual in that it enters host cells through caveolae and ends up in the endoplasmic reticulum. We now learn that the infectious route of SV40 is even more intriguing, as it proceeds through an entirely novel organelle, called the ‘caveosome’. Pelkmans and colleagues followed the intracellular route of Texas red-labelled SV40 by video-enhanced microscopy of live cells. They found that, after caveolar endocytosis, the virus arrives with relatively slow kinetics (20–40 min) in caveosomes — a new type of organelle that contains caveolin-1 but no markers of the classic endocytic or exocytic pathways. Caveosomes are dispersed throughout the whole cell and are not continuous with the extracellular space. They have irregular shapes and sizes, and, unlike organelles of the classic endocytic pathway, they have a non-acidic pH. SV40 remains for up to four hours in relatively static caveosomes before it is transported to the endoplasmic reticulum in much more dynamic tubular containers. Both budding and transport of these tubules depend on microtubules. Caveosomes are probably capable of molecular sorting, as SV40 is included in budding tubules but caveolin-1 is left behind (see picture). The authors suggest that caveosomes do not mature from caveolae but are independent organelles, which also exist in the absence of SV40 infection. So what do they do when they don’t have any viral passengers? Raluca Gagescu References and links ORIGINAL RESEARCH PAPER Pelkmans, L. et al. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nature Cell Biol. 3, 473–483 (2001)

MEMBRANE TRANSPORT of caveolins and caveolae. Last, Lamaze and colleagues showed that this endocytic pathway requires the GTPase ... and alternative pathways dynamin, and possibly polymerized actin, as active RhoA and Rac1 are necessary for effi- Any textbook will tell you that receptors are a protein required for clathrin-dependent cient endocytosis of IL2R. This is only the endocytosed from the plasma membrane in endocytosis, completely inhibits the uptake of beginning of a mechanism, but armed with a clathrin-coated vesicles. But is it really all the transferrin receptor (TfR) — a classical specific cargo (the IL2R), a few regulatory receptors? Apparently not, as Lamaze and col- marker of the clathrin pathway — but does proteins (dynamin and Rho GTPases) and leagues report in Molecular Cell that at least not affect IL2R endocytosis. In good agree- specific reagents to shut down the main path- one cellular receptor, the interleukin-2 recep- ment, immunoelectron studies revealed that way (Eps15 mutants), investigators should tor (IL2R), is endocytosed in a completely whereas TfR is concentrated in clathrin-coat- soon pierce the secrets of this mysterious clathrin-independent manner. ed lattices and vesicles, IL2R is clustered out- pathway. Although the only endocytic pathway side these structures. So is this endocytic route the same as the understood in some molecular detail is the Biochemical experiments indicated that previously described ‘alternative pathway’ clathrin pathway, it has been known for a long IL2R, but not TfR, is concentrated in deter- through which ricin is endocytosed? Also, we time that alternative endocytic pathways exist. gent-resistant membranes, which are consid- know that IL2R ends up in lysosomes where But such routes seemed to be chosen mostly ered to be the biochemical equivalent of cho- it’s degraded, but how does it get there after for dishonourable purposes, such as attacking lesterol and glycosphingolipid microdomains it’s internalized? And is IL2R a loner, going its cells with bacterial toxins (for example, ricin) (or lipid rafts). The association of IL2R with own way, or is it just the first of a crowd of or infecting them with viruses (SV40; see lipid rafts not only takes place at the plasma proteins that have gone unnoticed until now? Highlight above). IL2R is the first physiologi- membrane but also seems to persist inside the Raluca Gagescu cal cellular receptor that is endocytosed with- cell. Notably, endocytosis of IL2R does not References and links out the help of clathrin. occur through caveolae (see above) as many ORIGINAL RESEARCH PAPER Lamaze, C. et al. Interleukin 2 receptors and detergent-resistant membrane domains define a Lamaze and colleagues show that expres- of these experiments were done in lympho- clathrin-independent endocytic pathway. Mol. Cell 7, 661–671 sion of dominant-negative mutants of Eps15, cytes, which contain lipid rafts but are devoid (2001)