BBB seminar: Jaakko Saraste
Twenty years in the middle: Changing views of the intermediate compartment at the ER-Golgi boundary
Section of Anatomy and Cell Biology, Department of Biomedicine, University of Bergen
The intermediate compartment (IC) was first described twenty years ago as membranous structures in which transport of newly synthesized viral proteins between the endoplasmic reticulum (ER) and the Golgi apparatus is reversibly arrested at 15oC (1). Ever since their discovery these structures have been objects of intense study, resulting in a number of theories concerning their biogenesis, identity and relationship with the ER and Golgi. We know now that the IC consists of structurally and compositionally heterogenous elements which originate at widespread ER exit sites (ERES) and transport and sort proteins along with their microtubule-dependent movement to the central cis-Golgi region. However, whether these elements represent transient carriers devoted to protein transport or a more stable and functionally complex compartment is still debated.
We have recently examined the organization and dynamics of the IC in rat pheochromocytoma (PC12) cells that develop neuronal properties in response to nerve growth factor (NGF). These studies showed that the IC consists of two functionally distinct domains, one marked by the cargo receptor p58 and membrane-bound COPI coats, and the other by the GTPase Rab1. The striking finding was that the two IC domains segregate during the differentiation of these cells. The p58/COPI domain, like ER and Golgi membranes, remains in the cell body, whereas the tubular Rab1 domain moves to the growing neurites and accumulates in their growth cones. Thus, the Rab1-mediated pathway is unrelated to ER-Golgi transport, but is likely to function in neurite outgrowth by delivering membrane components from the early secretory route directly to the growth cones. Live cell imaging with fluorescent Rab1A showed that this pathway also exists in non-polarized cells. Our results (2) provide new insight into the dynamics and functional complexity of the IC and suggest that the organization of this compartment is regulated according to the developmental needs of the cell.
1. Saraste, J. and Kuismanen, E. (1984). Pre- and post-Golgi vacuoles operate in the transport of Semliki Forest virus membrane glycoproteins to the cell surface. Cell 38, 535-549.
2. Sannerud, R., Marie, M., Nizak, C., Pernet-Gallay, K., Perez, F., Goud, B., and Saraste, J. (2004). A novel Rab1-mediated transport pathway revealed in differentiating PC12 cells. Submitted for publication.