Compartmentalization of rab Proteins in Mammalian Cells

Classically, membrane-bound compartments have been viewed as comprising physically distinct entities each having a specific protein composition and characteristic functions. By this criterion, compartment boundaries should be easily delineated by ultrastructural localization of resident proteins. This simple view, however, is complicated by several factors. For example, even the localization of two proteins to different regions might not unequivocally demonstrate that they are present in physically discontinuous compartments. Such a distribution of proteins could reflect the existence of subdomains in an otherwise continuous membrane array. An example is the lateral heterogeneity found between the rough and the smooth endoplasmic reticulum (ER). Conversely, markers may be segregated into physically distinct membranes which nevertheless remain functionally continuous by repeated membrane fissions and fusions or transient tubular interconnections. The existence of such interactions among “like” elements would play an important role in preserving continuity among equivalent, but physically separated organelles. Furthermore, the definition of a compartment becomes more complicated if one considers organelles involved in membrane traffic. Given that membrane material is continuously transported and recycled between two organelles, precise biochemical definition of the compartments may be difficult. Some components are, of course, known to be resident, due perhaps to interactions with compartment-specific structural frameworks, and these can be used for compartment characterization. However, precise definition of the subcellular compartments requires detailed knowledge of the machinery regulating the entry and the exit of material at compartment boundaries, as well as the retention of molecules within the compartment (for further discussion see Mellman and Simons 1992). One family of proteins that may play an important role in defining compartment boundaries are the rab proteins, small GTPases that will be discussed in this chapter.