Neutrophils are the most abundant white blood cells in circulation, and patients with congenital neutrophil deficiencies suffer from severe infections that are often fatal, underscoring the importance of these cells in immune defense. In spite of neutrophils' relevance in immunity, research on these cells has been hampered by their experimentally intractable nature. Here, we present a survey of basic neutrophil biology, with an emphasis on examples that highlight the function of neutrophils not only as professional killers, but also as instructors of the immune system in the context of infection and inflammatory disease. We focus on emerging issues in the field of neutrophil biology, address questions in this area that remain unanswered, and critically examine the experimental basis for common assumptions found in neutrophil literature.

GCC185, a trans-Golgi network-localized protein predicted to assume a long, coiled-coil structure, is required for Rab9-dependent recycling of mannose 6-phosphate receptors (MPRs) to the Golgi and for microtubule nucleation at the Golgi via CLASP proteins. GCC185 localizes to the Golgi by cooperative interaction with Rab6 and Arl1 GTPases at adjacent sites near its C terminus. We show here by yeast two-hybrid and direct biochemical tests that GCC185 contains at least four additional binding sites for as many as 14 different Rab GTPases across its entire length. A central coiled-coil domain contains a specific Rab9 binding site, and functional assays indicate that this domain is important for MPR recycling to the Golgi complex. N-Terminal coiled-coils are also required for GCC185 function as determined by plasmid rescue after GCC185 depletion by using small interfering RNA in cultured cells. Golgi-Rab binding sites may permit GCC185 to contribute to stacking and lateral interactions of Golgi cisternae as well as help it function as a vesicle tether. INTRODUCTIONThe Golgi complex plays a central role in processing and sorting of secreted and membrane proteins. In mammalian cells, it is made up of a set of flattened cisternae that are organized as a stack (Farquhar and Palade, 1998). Within the Golgi, proteins undergo oligosaccharide side chain maturation, and they are sorted to different destinations, including apical or basolateral plasma membranes, prelysosomes, or secretory storage granules, as they exit this compartment.The Golgi surface is decorated with proteins called Golgins (Short et al., 2005;Sztul and Lupashin, 2006). Golgins are characterized by their predicted, highly extended, coiled-coil structures, and they typically have a high glutamic acid content (Ramirez et al., 2008). Certain Golgins have been implicated as transport vesicle tethers that help capture vesicles and bring them closer to their cognate targets; they are also essential for the maintenance of normal Golgi structure. For example, temperature-sensitive cells lacking GM130 have a disrupted Golgi at the nonpermissive temperature (Vasile et al., 2003); loss of Golgin-84 (Diao et al., 2003), Golgin-245 (Yoshino et al., 2005), TATA modulatory factor (Fridmann-Sirkis et al., 2004), GRASP55 (Feinstein and Linstedt, 2008), GRASP65 (Puthenveedu et al., 2006), and the so-called COG complex (Zolov and Lupashin, 2005) all lead to disruption of the Golgi ribbon. Thus, the Golgi complex is highly sensitive to the loss of any one of a large collection of Golgi-associated proteins.Most Golgins are peripherally associated with this organelle by virtue of interaction with small GTPases of the Rab and/or Arf (Arl) families; a few contain C-terminal membrane anchors (Short et al., 2005). Four human Golgins contain a so-called GRIP domain at their C termini that enables them to bind the Arl1 GTPase at the trans-Golgi network (TGN); Arl1 is essential for the Golgi targeting of multiple GRIP domain-containing proteins (Lu and Hong, 2003;Panic et al., 2003...

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A new paper from Campellone et al. in a recent issue of Cell identifies WHAMM, a multifunctional protein that stimulates Arp2/3-mediated actin polymerization, binds and organizes microtubules, and influences the structure and efficiency of the Golgi complex. WHAMM's membrane localization at the entry face of the Golgi complex is novel for an actin nucleation-promoting factor, and highlights the importance of the cytoskeleton in organizing the secretory pathway.