SNX18 promotes autophagosome formation by remodeling membranes and providing membrane to forming autophagosomes.

The molecular mechanisms implicated in endosomal sorting are currently attracting much attention and they have turned out to be more complex than first realized (Bonifacino and Rojas, 2006;Maxfield and McGraw, 2004). A number of different factors are required to support the sorting decisions that have to be made to ensure that different cargoes are taken to the appropriate destinations according to the needs of the cell. Transport intermediates can either be in the form of round vesicles or extended tubules, and some cells display an elaborate system of endocytic membrane networks that are thought to be involved in specific trafficking events. The dynamic organelles commonly referred to as early endosomes appear to be major sorting stations within the system, and can be functionally divided into sorting endosomes and recycling endosomes. Internalized material can either recycle back to the plasma membrane by one of several routes, be sorted to the transGolgi network (TGN) or end up in the lysosomal pathway leading to degradation of the cargo.Membrane-binding and -modulating proteins are important for the mechanics of the endocytic system. Classical examples are the vesicular coat proteins, such as clathrin and its adaptor proteins (APs) (Edeling et al., 2006b;Robinson, 2004;Ungewickell and Hinrichsen, 2007). Clathrin acts as a vesicular stabilizing protein at several locations in the cell, and clathrin-dependent carrier formation requires membrane-specific APs for localization, coat assembly, accessory protein recruitment and cargo selection. There are four different kinds of APs, which operate at diverse cellular sites. For example, whereas AP-2 is mostly found at the plasma membrane participating in clathrin-dependent endocytosis, AP-1 is concentrated at the TGN to mediate clathrin-dependent trafficking of cargo to the endosomal system. AP-1 is also found on endosomal membranes and is proposed to take part in trafficking pathways for retrieval of cargo to the TGN. However, it is unclear how the same AP can work in trafficking pathways that go in opposite directions. An arrangement like this would probably require different procedures for carrier formation, to give unique identities of the transport intermediates. Such differences might be mediated by specific accessory proteins and membrane-modulating proteins. The advantage of using the same cargo-binding adaptor for anterograde and retrograde traffic is that efficient recycling systems can be created for proteins that shuttle between compartments, such as the mannose 6-phosphate receptor and furin.Proteins that can bind and modulate specific membrane zones are important players in the process of vesicular-and tubular-carrier formation. Examples are proteins with phosphoinositide-binding PX (phox homology) and PH (pleckstrin homology) domains (Di Paolo and De Camilli, 2006;Lemmon, 2003), as well as proteins with membrane-bending function (Zimmerberg and Kozlov, 2006). A class of proteins with the latter property is the recently described BAR (Bin/Amphiphysin/...