title: Cdc42 interacts with the exocyst complex to promote phagocytosis.
abstract: The process of phagocytosis in multicellular organisms is required for homeostasis, clearance of foreign particles, and establishment of long-term immunity, yet the molecular determinants of uptake are not well characterized. Cdc42, a Rho guanosine triphosphatase, is thought to orchestrate critical actin remodeling events needed for internalization. In this paper, we show that Cdc42 controls exocytic events during phagosome formation. Cdc42 inactivation led to a selective defect in large particle phagocytosis as well as a general decrease in the rate of membrane flow to the cell surface. Supporting the connection between Cdc42 and exocytic function, we found that the overproduction of a regulator of exocytosis, Rab11, rescued the large particle uptake defect in the absence of Cdc42. Additionally, we demonstrated a temporal interaction between Cdc42 and the exocyst complex during large particle uptake. Furthermore, disruption of exocyst function through Exo70 depletion led to a defect in large particle internalization, thereby establishing a functional role for the exocyst complex during phagocytosis.
authors.affiliation: Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Sina
authors.initials: S
authors.lastname: Mohammadi
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D046912:Multiprotein Complexes; D033921:Vesicular Transport Proteins; D020764:cdc42 GTP-Binding Protein; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C547754:EXOC7 protein, human; C522783:Exo70 protein, mouse